rock%lighthouse%pyrdc%wubios@uunet.UU.NET (Roger Rock Rosner) (10/29/89)
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TREATMENT - Table of Contents August 1989 - Vol 1, No 3
Anti-retroviral protocols
Alpha Interferon and Interleukin-2
Alternating/Intermittent AZT and ddC (ACTG 047)
AS-101 and AZT
AzdU
AZT and Acyclovir (ACTG 063)
AZT and Alpha Interferon
AZT and GM-CSF
AZT and Interleukin-2
AZT for Veterans
AZT in Hemophiliacs (ACTG 036)
AZT, Alpha Interferon, and GM-CSF
Betaseron and Reduced Dose AZT
ddI (2',3'-dideoxyinosine)
Recombinant Soluble CD4
Pneumocystis carinii Pneumonia (PCP) protocols
Dapsone or Dapsone/Pyrimethamine
Piritrexim and leucovorin
CMV Retinitis protocols
Foscarnet
Gancicyclovir (ACTG 071)
Toxoplasmosis protocols
Pyrimethamine and Dapsone
Miscellaneous protocols
Blood Drawing Study
Bronchoalveolar Lavage Study
Bronchoscopy Study
gp-160 (Vaccine)
HIV & Heart Disease Study
Megace
Other protocols
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ANTI-RETROVIRAL PROTOCOLS
----------------------------------
ALPHA INTERFERON AND INTERLEUKIN-2
DESCRIPTION: An evaluation of the toxicity and effectiveness of the
combination of alpha interferon and interleukin-2 in the treatment of
patients with HIV infection.
REQUIREMENTS: Participants must: have evidence of HIV demonstrated by
ELISA and Western Blot or a positive culture for HIV; have a T4 cell count
of greater than or equal to 200/mm^3; be between the ages of 18 and 60; and
not have been exposed to chemotherapy, corticosteroid therapy or
experimental therapy for six weeks prior to entry. A negative pregnancy
test is required for women of child-bearing potential. All participants
must have a primary physician involved and available to communicate with NIH
staff during the study.
TERM: As an outpatient during the time it takes to gradually increase alpha
interferon doses to a maximum level, and hold the dose at maximum for two
weeks. As an inpatient, an additional 21 days of IL-2 infusion, with
outpatient follow-up visits for the next two months.
ADMINISTRATION: Alpha interferon is self-administered by the patient by
daily injection under the skin (much the same as the method used by
diabetics). Interleukin-2 is administered by injection into the vein
continuously for 21 days. There are weekly and bimonthly blood drawings and
clinic visits during the term of the study.
METHODOLOGY: Both alpha interferon and interleukin-2 are well-tolerated as
individual drugs in HIV-infected persons. Researchers are trying to
determine whether the use of both drugs simultaneously will result in
beneficial effects not seen in either when taken as single agents, and what
the side effects are of the combination.
NOTES: Potential side effects of alpha interferon include flu-like
symptoms, a decrease in white cells, mental changes, gastrointestinal
disturbances, temporary hair loss, minor liver problems, and congestive
cardiomyopathy. Interleukin-2 has also been associated with some side
effects such as proteinuria, mild prolongation of PTT, fever, hepatitis,
rigors, increased incidence of bacterial infection, and eosinophilia. All
these effects improved or disappeared after discontinuation of the drugs.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
ALTERNATING AND INTERMITTENT DOSES OF 2',3'-DIDEOXYCYTIDINE (DDC) AND AZT IN
PATIENTS WITH AIDS AND ARC WHO ARE NOT ON AZT (ACTG 047)
DESCRIPTION: To determine if alternating AZT and ddC (first one, then the
other) or intermittent therapy (one week on, one week off) with either drug
will decrease the side effects of either drug alone, while still suppressing
HIV.
REQUIREMENTS: Two groups of patients will be admitted to the study, one
with ARC, the other with AIDS.
Patients with ARC must have the documented presence of at least one of the
following: weight loss in excess of 15 pounds or 10 percent of body weight
within 120 days of the study; temperature greater than 38.5 degrees C (about
100 degrees F) with or without night sweats, persisting for more than 14
consecutive days or more than 15 days in a 30-day interval prior to entry
into the study; diarrhea which is defined as three or more liquid stools per
day, persisting for more than 30 days prior to entry into the study without
definable cause; recurrent oral candidiasis (thrush in the mouth); hairy
leukoplakia (white bumps which appear on the tongue and in the mouth); or a
history of Herpes Zoster (Shingles).
Patients with AIDS qualify for the study if they have CDC-defined AIDS
(fulfill the Surveillance Definition of the Centers for Disease Control),
and do not require systemic maintenance chemotherapy.
All patients (ARC and AIDS), in order to qualify for the study, must also
have a consistently positive p24 antigen test (at least 70 picograms/ml,
defined by the Abbott HIV antigen test). This means the participant must
have a positive p24 antigen test seen on two occasions, each within one
month prior to entry in the study, separated by at least 72 hours, and the
last of these observations must occur within two weeks of starting the
therapy (any negative antigen test during this period will exclude the
patient from the study). All participants must also have: a positive ELISA
HIV test; the ability to care for most personal needs requiring at most
occasional assistance; attained the age of 13 years (those between 13 and 18
must have written consent by parent or legal guardian); if a woman of child-
bearing potential, must have a negative pregnancy test within 30 days of
entry in the study and use an effective method of birth control during the
study.
All participants must also have laboratory values within certain limits:
hemoglobin of at least 9.6 g/dl (patients requiring transfusions of two
units of blood more than once a month are excluded and the last transfusion
must occur before two weeks prior to entry); granulocyte count of at least
1200 cells/mm^3; platelet count of at least 100,000/mm^3; calculated
creatinine clearance greater than 50 ml/min/1.73m^2; and transaminase less
than five times the upper limit of normal.
Patients with ARC will be excluded from the ARC study group if they have an
opportunistic infection or malignancy (tumor) fulfilling the definition of
AIDS, or have neoplasms (cancerous growths) other than basal cell carcinoma
of the skin or in-situ carcinoma of the cervix.
Patients with AIDS will be excluded from the study: if they have an active
opportunistic infection and require ongoing systemic therapy and/or
prophylaxis for an AIDS-defining opportunistic infection (an exception is
the use of inhaled aerosolized pentamidine as a preventive for Pneumocystis
Carinii pneumonia); if they have symptomatic visceral Kaposi's sarcoma (KS),
progression of KS within one month prior to entry in the study or with
neoplasms other than KS, basal cell carcinoma of the skin or in-situ
carcinoma of the cervix; or if they require antineoplastic therapy.
Patients with either AIDS or ARC will be excluded if they: demonstrate
significant malabsorption (a condition in which the body does not properly
absorb nutrients or drugs); are active substance abusers; have received any
antiretrovirals within 60 days prior to entry or have received biological
modifiers or corticosteroids within 30 days prior to entry; have significant
cardiac, liver, or neurologic disease; suffer from diabetes, kidney failure,
or alcoholism or take neurotoxic drugs such as dapsone or nitrofurantoin;
have previously taken ddC; have experienced dose-limiting or transfusion-
requiring toxicity during a previous course of AZT therapy; have a history
of Idiopathic Thrombocytopenic Purpura; require prolonged acyclovir therapy;
are women who are pregnant or are breast feeding; or are unwilling to be
followed by the medical center during the study and follow-up.
ADMINISTRATION: A total of 112 patients will be divided, randomly, into
seven different treatment regimens. All medication will be given orally,
and all patients completing the study will be followed for four weeks after
completion.
The seven groups of the study are described below:
1. Weekly Alternating. AZT is administered at 200 mg every four hours for
one week, after which AZT is stopped and ddC administration begins at 0.01
mg/kg every four hours for one week, for 24 full cycles, or 48 weeks, of
therapy administered.
2. Weekly Alternating (different dose of ddC). AZT is administered at 200
mg every four hours for one week, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one week, for 24
full cycles, or 48 weeks, of therapy administered.
3. Monthly Alternating. AZT is administered at 200 mg every four hours
for one month, after which AZT is stopped and ddC administration begins at
0.01 mg/kg every four hours for one month, for six complete cycles, or 48
weeks, of therapy administered.
4. Monthly Alternating (different dose of ddC). AZT is administered at
200 mg every four hours for one month, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one month, for six
complete cycles, or 48 weeks.
5. Intermittent AZT. AZT is administered at 200 mg every four hours for
one week, then AZT is stopped and no drug is given for one week. After a
week with no drug, AZT is again administered for a week, for 24 cycles, or
48 weeks. No ddC is given to this group.
6. Intermittent ddC. ddC is administered at 0.03 mg/kg every four hours
for one week, alternating with one week of no drug. A total of 24 cycles,
or 48 weeks, of one week on ddC and one week with no drug will take place.
No AZT will be given to this group.
7. Continuous AZT. AZT will be administered at 200 mg every four hours
for 52 consecutive weeks. No ddC will be given to this group.
TERM: 52 weeks
METHODOLOGY: Both AZT and ddC are potent inhibitors of HIV. They are Chain
Terminators, which means they interfere with the ability of HIV to
replicate. Both these drugs place the patient at risk for serious, but
different, side effects. Researchers hope to demonstrate through this study
that alternating the use of the two drugs will reduce the side effects while
maintaining the positive aspects of HIV inhibition.
CONTROLS: None
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Mary Beth Goldin, George Washington University AIDS Clinical
Trials Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202)
994-2417
----------------------------------------
AS-101 AND AZT
DESCRIPTION: Phase I open label, dose-escalation study designed to obtain
toxicity data and preliminary data on the immunologic, anti-viral and
clinical effects of AS-101 in combination with zidovudine (AZT) in patients
with HIV infection and CD4 counts less than 200/mm^3 (or 20% of
lymphocytes).
REQUIREMENTS: Participants must be: HIV infected; 18-60 years of age; able
to provide informed consent; free from active infection or illness requiring
specific therapy that could interfere with protocol; able to tolerate AZT
100 or 200 mg every four hours or have no prior history of AZT intolerance,
and have a CD4 count less than 200/mm^3 or less than 20% of circulating
lymphocytes. Those with a history of intolerance to aerosolized pentamidine
are excluded.
TERM: 12 weeks of outpatient drug therapy if currently on AZT; otherwise
six weeks of AZT followed by 12 weeks of combination therapy.
ADMINISTRATION: This is a dose escalation study with participants receiving
escalating doses of AS-101 in combination with AZT. Participants will be
enrolled sequentially in groups of five, receiving AS-101 intravenously at
doses of 3, 5, or 8 mg/M^2 three times a week and AZT 100 or 200 mg orally
every four hours depending on tolerance for 12 weeks. The drug infusions
will take 15-60 minutes depending upon dosage. Three participants from each
dose group will be treated for a minimum of four weeks before patients are
entered at the next higher dose level.
Participants not previously treated with AZT will be started at 200 mg
orally every four hours, decreased to a minimum of 100 mg every four hours
if necessary. All participants will be required to receive at least six
weeks of AZT at a minimum of 100 mg every four hours prior to starting AS-
101.
Participants will also receive aerosolized pentamidine 300 mg every four
weeks during the study period for prophylaxis against pneumocystis.
METHODOLOGY: AZT is a potent inhibitor of HIV, however it does not reverse
the immunodeficiency associated with HIV infection, and progressive disease
frequently occurs. AS-101, a synthetic compound, has been found in vitro to
increase the response to and production of interleukin-2, a lymphokine with
immune-modulating properties. Thus, a combined regimen of AZT with AS-101
may provide some anti-retroviral and immunomodulatory activity.
NOTES: Possible side effects of AZT include nausea, headache, anemia,
decrease in white cells, and myopathy. AS-101 can cause lightening and
thinning of hair, garlic body odor, rash, nausea, headache, and
abnormalities of the urine.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
AZDU
DESCRIPTION: Phase I/II study of 3'-Azido-2',3'-dideoxyuridine (AzdU) in
people with HIV infection.
REQUIREMENTS: Participants in this study must be positive on the ELISA and
the Western Blot, and have a CD4 (T4) count between 200 and 400/mm^3.
Participants must be over age 18, have no previous use of AZT, have good
veins, and be willing to come to NIH for weekly blood drawing and clinic
visits. Participants must also have a private physician involved in their
care and available for communication with the NIH doctors and nurses during
the time they are on this study.
TERM: 14 1/2 weeks, with participants who show a beneficial response having
the option to continue treatment after the study period ends.
ADMINISTRATION: Participants will be divided into one of five groups who
will receive different dosages of AzdU. The first dose will be given
intravenously over one hour at the Clinical Center at NIH, with frequent
blood drawing to measure drug levels. Two days later, a single oral dose
will be given to measure oral absorption. Two weeks later, a twelve week
period of oral dosing of the drug will begin. There will be frequent
sampling of blood and urine during the course of the study for monitoring
and evaluation to minimize potential toxicities. Participants will be
assessed monthly for three months, and then every three months after being
on the drug for nine months.
METHODOLOGY: AzdU is a Chain Terminator, a "nucleoside analog" similar to
AZT. It works by interfering with the ability of HIV to replicate.
NOTES: AzdU has not been given to humans before, so potential side effects
are unknown. Animal studies have shown toxicities only at extraordinarily
large doses. Other nucleoside analogues have caused elevations of liver
function tests, nausea, headache, and bone marrow suppression. A total of
15 people will be enrolled in this study.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID), Laboratory of Immunoregulation
CONTACT: Dianne Lee, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
AZT AND ACYCLOVIR (ACTG 063)
DESCRIPTION: A double-blind phase II/III study of different dosages of AZT
and acyclovir in patients with AIDS.
REQUIREMENTS: Participants must have been diagnosed with AIDS within the
past four months, as defined by CDC category IV-C-1, i.e. with PCP,
cryptosporidiosis, toxoplasmosis, extraintestinal strongyloidiasis,
isosporiasis, candidiasis (esophageal, bronchial, or pulmonary),
cryptococcosis, histoplasmosis, mycobacterial infection, cytomegalovirus,
mucocutaneous or disseminated herpes simplex virus, or progressive
multifocal leukoencephalopathy. Participants must also: be positive on the
ELISA and the Western Blot; be greater than 13 years of age; and be able to
take care of themse lves requiring only occasional assistance. Women of
childbearing potential must have a negative pregnancy test within 30 days of
the start of the study and be willing to practice a barrier method of
contraception while on the study. Laboratory tests must also be within
certain limits (total neutrophil count greater than 1000/mm^3; platelet
count greater than 50,000 cells/mm^3; hemoglobin greater than 9.0 mg/dl, and
the patient cannot be transfusion dependent--the last transfusion must be at
least two weeks prior to the study; serum creatinine less than 1.5 times the
upper limit of no rmal or clearance greater than 50 ml/min; SGOT less than
five times the upper range of normal).
People will be excluded who: have symptomatic visceral or progressive
Kaposi's sarcoma (defined by more than 10 new lesions in the 30 days prior
to the study); have neoplasms other than basal cell carcinoma of the skin;
are pregnant women, nursing mothers, or women not employing birth control or
abstinence; have malabsorption as defined by persistent diarrhea greater
than six stools/day for more than four weeks; require acyclovir prophylaxis
or frequent (more than once a month) courses of acyclovir therapy for herpes
simplex virus infection, however episodic treatment with acyclovir is
permitted; have received systemic acyclovir therapy within 14 days of the
start of the study; have been previously treated with AZT for more than 120
days; have received other anti-retrovirals within 30 days of study entry;
have received ribavirin within 60 days of study entry; have received
cytotoxic chemotherapy or radiation therapy for KS within 30 days of study
entry; are participating in a protocol which compares AZT to a placebo (e.g.
ACTG 016 and ACTG 019); or are active substance abusers (methadone
maintenance therapy is permitted).
TERM: Two years
ADMINISTRATION: Participants will be divided into four groups: the first
group will get 1000 mg/day of AZT and no acyclovir; the second will get 500
mg/day of AZT and no acyclovir; the third will get 1000 mg/day of AZT and
4000 mg/day of acyclovir; and the fourth will get 500 mg/day of AZT and 4000
mg/day of acyclovir. All medication will be taken orally, every four hours
while awake (five times a day). Participants will have to come in once
every two weeks for a clinic visit. If participants demonstrate significant
toxicity, the dosage may be modified, or the therapy stopped.
METHODOLOGY: There has been some conjecture that Human Herpes Virus Six
(HHV-6) may activate HIV. Since acyclovir is an effective drug against the
whole Herpes family of viruses, it is hoped that the combination of AZT,
which has been shown to inhibit HIV replication, with acyclovir may have a
greater effectiveness with fewer side effects than either drug taken alone.
It may also allow for a lower dose of AZT while still being effective
against HIV. The negative side effects of AZT have been shown to be dose-
related, so the combination therapy of AZT and acyclovir may allow eff
ective treatment with fewer side effects (primarily bone marrow suppression)
from AZT.
NOTES: Possible side effects include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. Acyclovir has some of the same side effects as
AZT, and also anorexia (loss of appetite).
CONTROLS: None. All participants are guaranteed to receive some dosage
level of AZT, and half the participants will receive some dosage level of
acyclovir.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Kathryn Grabowy, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
----------------------------------------
AZT AND ALPHA INTERFERON
DESCRIPTION: Study of AZT alone vs. AZT and Alpha Interferon vs. Alpha
Interferon alone, for people in the early stages of HIV infection.
REQUIREMENTS: Positive lymphocyte culture for HIV, or positive p24 antigen
test, or positive PCR test, and T4 cell counts of more than 500 per cubic
millimeter. Participants must be over age 18, have not participated
previously in any other HIV protocols, have good veins, and be willing to
come to NIH for weekly to biweekly blood drawing and clinic visits.
Participants may have been on AZT before. Participants must also have a
private physician involved in their care and available for communication
with the NIH doctors and nurses during the time they are on this study.
TERM: Indefinite. The study continues until the participant develops an
opportunistic infection, their T4 cell counts drop below 200, or the
participant develops severe side-effects or reactions (toxicity) to either
of the medications.
ADMINISTRATION: Participants will be divided into three groups: one will
receive AZT alone, one will receive AZT and alpha interferon, and the last
will receive alpha interferon alone. AZT is given orally; alpha interferon
is given by injection. Persons enrolled in the study will be taught to give
the alpha interferon to themselves. The AZT-only group will take 200 mg
every four hours. The AZT/alpha interferon group will take 100 mg of AZT
every 4 hours and 1 million units of alpha interferon every day. The alpha
interferon-only group will initially receive 5 million units e very day.
The doses of alpha interferon will be increased, as tolerated, to a maximum
of 35 million units per day.
METHODOLOGY: AZT is a "nucleoside analog" (a fake version of the base
thymidine) which interferes with the ability of HIV to make copies of
itself. Alpha Interferon interferes with the final assembly process of HIV
which happens as HIV tries to bud off new copies of itself into the
bloodstream.
NOTES: Potential side effects of AZT include nausea, headaches, fatigue,
and anemia that may require blood transfusion. Alpha interferon can cause
flu-like symptoms (fevers, fatigue, muscle aches, decrease in appetite), a
decrease in white blood cell count, and mental changes, including
depression, memory loss, and difficulty concentrating.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID), Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
AZT AND GM-CSF
DESCRIPTION: Phase I study of AZT (Azidothymidine) combined with GM-CSF
(Granulocyte/Macrophage-Colony Stimulating Factor) in patients with AIDS or
symptomatic HIV infection.
REQUIREMENTS: All participants must be at least 18 years old and have T4
cell counts of less than 200. Participants must have either never taken
AZT, or have taken at least 600 mg a day, and discontinued because of
toxicity to the patient's white blood cells. Participants who were on AZT
must be off it for at least four weeks prior to the study. All participants
must have a white blood cell count of less than 3,000 per cubic millimeter
and hemoglobin of greater than nine grams per deciliter. All participants
must have greater than 75,000 platelets per cubic millimeter and no t
ransfusions within the past month. People with active opportunistic
infections are excluded from the study. No other cytotoxic or
antiretrovirals may be taken while participants are in the protocol,
although prophalaxis for PCP with either Fanzidar, Bactrim, or aerosolized
Pentamidine is permitted. Women of child-bearing potential must have a
negative pregnancy test prior to the start of the study, and be willing to
use birth control measures during and for two months after the study.
TERM: 12 months, with the possibility of an extension if the patient
responds favorably to the treatment. All treatment is on an outpatient
basis from the NIH Clinical Center.
ADMINISTRATION: The AZT is given orally every four hours; the GM-CSF is
given two times a day by a self-administered injection just under the skin
(similar to the way insulin is self-injected by diabetics).
METHODOLOGY: AZT, while effective at suppressing the reproduction of HIV,
has an unfortunate side effect of suppressing the production of granulocytes
and macrophages, which are types of white blood cells, within the bone
marrow. GM-CSF stimulates the production of granulocytes and macrophages,
so it is hoped that by taking GM-CSF in combination with AZT, AZT's toxic
side effects can be reduced or eliminated, or that a larger dose of AZT with
tolerable side effects will be possible.
NOTES: If the patient's white cell counts fall while he/she is in the
study, the dosage of GM-CSF will be increased (two increases only) to try to
counter the toxicity problems.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drugs.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. James Pluda, Building 10, Room 13N248, National institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-8398
----------------------------------------
AZT AND INTERLEUKIN-2
DESCRIPTION: The study will evaluate the effectiveness and toxicity of the
combination of AZT (also known as zidovudine and Retrovir) and Interleukin-2
(IL-2) in the treatment of persons with HIV infection.
REQUIREMENTS: To be eligible to participate in the study, a person must
have HIV diagnosed by ELISA and Western Blot or a positive culture. The
person must not have had any of the opportunistic infections associated with
AIDS and must have over 200 T4 cells per cubic millimeter. If the person is
receiving AZT, he/she must be able to tolerate 200 mg every four hours.
TERM: Seventeen weeks (with possible extension of therapy if significant
improvement occurs).
ADMINISTRATION: AZT alone will be given for six weeks (orally). Following
that, AZT and IL-2 will be administered for three weeks. The IL-2 will be
administered IV continuously for three weeks and this part of the study will
be done on an inpatient basis. In addition there will be weekly or biweekly
blood drawing for the duration of the study.
METHODOLOGY: Studies have demonstrated that AZT can decrease the frequency
of opportunistic infections, but it sometimes results in bone marrow
suppression. IL-2 is a drug which stimulates the immune system.
Researchers are trying to determine whether the IL-2 might reduce the side
effects of AZT, thus allowing more patients to take full doses of AZT.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
AZT FOR VETERANS
DESCRIPTION: Study of the effectiveness of AZT in a double-blind,
controlled study of patients with ARC (AIDS Related Complex).
REQUIREMENTS: Participants in the study must be VA eligible. They must be
HIV antibody positive, with T-cell counts between 200 and 500, and they must
have some minor symptoms.
TERM: The protocol lasts for three years.
ADMINISTRATION: The study drug is taken orally in 250 mg doses every four
hours, around the clock.
METHODOLOGY: AZT is a Chain Terminator, which means it interferes with the
ability of HIV to replicate. This study attempts to determine to what
extent AZT helps people with ARC.
CONTROLS: This is a double-blind, randomized, controlled study. This means
that 50% of the participants will get AZT, and THERE IS A 50% CHANCE THAT
THEY WILL NOT. No one (neither the researchers nor the patient) will know
who is or who is not on AZT.
ORGANIZATION: Veterans Affairs Medical Center
CONTACT: Pat Kramer or John Scott, Veterans Affairs Medical Center, 50
Irving Street, N.W., Washington, DC 20422, (202) 745-8694
----------------------------------------
AZT IN HEMOPHILIACS (ACTG 036)
DESCRIPTION: This is a double-blind placebo-controlled study to determine
whether AZT (also known as zidovudine or Retrovir) will delay or alter the
progression of disease in HIV infected hemophiliacs.
REQUIREMENTS: Participants must: have HIV infection confirmed by Western
Blot; be at least 12 years old; and have been diagnosed with hemophilia, Von
Willebrand's Disease, or other coagulation-deficient disorders.
Participants must have laboratory results within certain limits:
granulocyte count of at least 1000 cells/mm^3; platelet count of a least
75,000/mm^3; hematocrit greater than 30 percent; creatinine less than or
equal to 1.5 times normal or clearance of at least 50 ml/min; and
transaminases less than or equal to five times the upper limit of normal.
Participants must al so have a Karnofsky performance status of 90 (able to
carry on normal activity; minor signs or symptoms or disease), although if
this measure is impaired by hemophilia complications, a status as low as 60
will be accepted (requires occasional assistance but is able to care for
most of his/her needs).
Patients will be excluded from the study if there is a history of AIDS
defining infection or malignancy or an unexplained temperature higher than
38oC (about 100.5oF) for more than five consecutive days or on more than 10
days in any 30-day period in the two years before entering the study.
Additional exclusions are: unexplained severe diarrhea; unintentional
weight loss of more than 10 percent of body weight in the past two years;
oral hairy leukoplakia (white spots or patches on the tongue or cheek); a
history of oral candidiasis not related to antibiotics; or herpes zoster
infec tion within the past two years. People will also be excluded if:
they have taken antiretroviral agents (like AZT) within the last eight weeks
or immunomodulating drugs (like steroids); they have taken other
experimental therapy within three months; or if they require therapy with
isoniazid or rifampin. All participants will be required to practice
effective contraception, and pregnancy is a basis for exclusion from the
study.
TERM: Up to three years
ADMINISTRATION: Participants will take orally three 100 mg capsules every
four hours for five doses per day. Half of these persons will be receiving
AZT, the other half will be receiving a harmless placebo.
METHODOLOGY: AZT acts on HIV to inhibit its replication (reproduction or
copy of itself). It is a Chain Terminator.
CONTROLS: This is a double-blind, placebo-controlled study, which means 50%
of the patients will get AZT, and 50% WILL GET NONE. Neither the patient
nor the researchers will know which is which during the course of the study.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Stacy Russell, George Washington University Hematology/Oncology
Clinic, 2150 Pennsylvania Avenue, N.W., Washington, DC 20037, (202) 994-
4200
----------------------------------------
AZT, ALPHA INTERFERON, AND GM-CSF
DESCRIPTION: This study is designed to evaluate the safety and
effectiveness of giving recombinant granulocyte-macrophage colony
stimulating factor (GM-CSF) in combination with AZT and alpha interferon in
patients with HIV infection.
REQUIREMENTS: Participants must: be over age 18; have a CD4 count of 200
to 500 per cubic millimeter; be positive for HIV on both the ELISA and the
Western Blot; have good veins; and be under the care of a physician with
whom the researchers can communicate while they are on the study. People
with active opportunistic infections are excluded.
TERM: Sixteen weeks after the dosages have stabilized, all of which is
outpatient.
ADMINISTRATION: Newly enrolled patients will be divided into two groups.
One group will receive 100 mg of AZT orally every four hours for four weeks,
and then will begin on interferon with 10 million units/day by injection
under the skin with the dose escalating by five million units/day every two
weeks. When the granulocyte count falls below 1000/mm^3, GM-CSF will be
started at a dose of one microgram (ug) per kilogram of body weight per day
(ug/kg/day), by injection under the skin. The GM-CSF dose will be escalated
to maintain the granulocyte count over 1500/mm^3. Once the patient's
granulocyte count is stable on AZT, interferon, and GM-CSF, the patient will
be treated for 16 weeks. The second group is identical to the first, except
their starting AZT dose will be 200 mg every four hours. Enrollment will be
done sequentially--the first 10 patients will be in the first group, and the
second 10 will be in the second group.
NIH patients who have previously been on combination AZT/interferon therapy
will comprise a third group. Patients in this group will begin on AZT and
interferon at the doses at which they became granulocytopenic (low counts of
granulocytes) in the past, with GM-CSF at one mg/kg/day starting at the same
time. Doses of AZT, interferon, and GM-CSF will be escalated, as tolerated,
in an attempt to bring the patients up to an optimal dosing level of AZT 200
mg every four hours and interferon 10 million units per day. The treatment
period for the third group, once the patient's granulocyte count is
stabilized above 1500/mm^3, will also be 16 weeks.
METHODOLOGY: While studies in the laboratory and in humans have shown that
AZT and alpha interferon given together can inhibit HIV, up to 50% of
patients taking this combination of drugs develop granulocytopenia, a
potentially serious decrease in a particular infection-fighting white blood
cell known as the granulocyte. Granulocyte-macrophage colony stimulating
factor is a bone marrow growth factor that stimulates production of several
types of cells found in blood, including the granulocyte.
NOTES: Potential side effects of AZT include nausea, headaches, and anemia
that may require blood transfusion. Interferon can cause flu-like symptoms
(fevers, fatigue, muscle aches, decrease in appetite), a decrease in white
blood cell count, and mental changes, including depression, memory loss, and
difficulty concentrating. The combination of AZT and interferon has been
known to cause a decrease in granulocytes and depression of liver function.
GM-CSF can cause fever, bone pain, and flu-like symptoms in some patients.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases, Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
BETASERON (BERA INTERFERON) AND REDUCED DOSE AZT IN AIDS AND ADVANCED ARC
PATIENTS
DESCRIPTION: Comparative study of high dose Betaseron, low dose Betaseron,
or placebo in combination with reduced dose AZT.
REQUIREMENTS: Patients must have: laboratory evidence of HIV infection;
either AIDS by CDC criteria or documentation of an absolute T4 count less
than 200; a reaction to AZT that requires dose reduction of AZT to 500-600
mg of AZT daily and the ability to tolerate this reduced dose; Karnofsky
status of 60 or greater (be able to take care of daily needs requiring only
occasional assistance); acceptable renal (kidney) function; acceptable
hepatic (liver) function; attained at least age 18; be available for follow-
up; and be willing to continue on reduced dose AZT at own expense.
Participants must have laboratory results within certain limits:
granulocyte count currently greater than 1000/mm^3; hemoglobin greater than
8.5 mg/dl; and platelet count greater than 50,000/mm^3. People will be
excluded if they have: ineffectively controlled opportunistic infections;
Kaposi's sarcoma requiring systemic chemotherapy; cytotoxic chemotherapy
within 30 days of the first Betaseron dose; proteinuria of 2+ or greater;
concurrent therapy with anti-virals other than AZT or Betaseron; chronic
concurrent therapy with acyclovir; prior therapy with interferon; HIV
encephalopathy (dementia); HIV wasting syndrome; pregnancy or lactation
(women with childbearing potential must take adequate precautions to prevent
pregnancy during treatment); active drug or alcohol abuse; New York heart
classification III or IV; uncontrolled angina pectoris (severe pain about
the heart, usually travelling down the left arm); or evidence of clinically
significant multifocal uncontrolled cardiac dysrhythmias.
TERM: Indefinite. The study will continue until the superiority of the
treatment is clearly demonstrated or disproved.
ADMINISTRATION: All patients continue on reduced dose AZT. Each patient is
assigned to one of three treatment groups--high dose Betaseron, low dose
Betaseron, or placebo. The patient administers daily injections of the
study drug into the skin (in the same way that diabetics inject themselves).
The patient must visit the test site for lab and physical evaluations once a
week for a month, biweekly for two months, and monthly thereafter.
METHODOLOGY: Many patients on AZT develop side effects which involve the
blood and must, therefore, be put on a reduced dose of AZT. In the
laboratory, Betaseron (a recombinant form of interferon Beta) has been shown
to enhance the action of AZT in blocking the ability of the HIV to make
copies of itself, to kill lymphocytes, and to spread between lymphocytes.
In clinical studies, patients who have taken Betaseron have shown evidence
of suppression of the HIV copying mechanism and a low incidence of
opportunistic infections. Although there may be side effects from
Betaseron, they are seldom related to the blood. As a result, researchers
believe that a level of AZT which is not toxic to the patient might be
combined with Betaseron to get positive results similar to a higher AZT dose
without the negative side effects of AZT on the blood.
NOTES: Possible side effects of Betaseron include mild flu-like symptoms
and redness at the injection site. These effects generally decrease and
disappear with continuing treatment. Sometimes a mild depression in blood
cell counts occurs.
CONTROLS: Two out of three patients will be given Betaseron, with the third
patient on a placebo. Although the study is placebo controlled, it should
be noted that all patients will be maintained on low doses of AZT, thus
ensuring that all patients will be receiving at least some anti-viral
therapy.
ORGANIZATION: George Washington University Hospital
CONTACT: Grace Gianturco, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
----------------------------------------
DDI (2',3'-DIDEOXYINOSINE)
DESCRIPTION: Phase I Study of drug to fight HIV.
REQUIREMENTS: This study is for people with AIDS or severe ARC,
PARTICULARLY PEOPLE WHO HAVE NOT BEEN ON AZT OR HAVE BEEN ON AZT FOR SIX
WEEKS OR LESS. Participants must be off AZT and other anti-viral therapy
for at least four weeks before the study. All participants must have a
count of less than 350 T4 cells per ml, and must not be anemic or have a low
white blood count. ARC patients must have either oral thrush or weight
loss. People with severe Kaposi's sarcoma or active opportunistic
infections are excluded.
TERM: The initial phase lasts for a total of 13 months; two weeks as an
inpatient and 12 1/2 months as an outpatient. If the initial results prove
favorable, it is possible that permission will be obtained from the FDA to
continue the study for a longer period of time.
ADMINISTRATION: On the first day, the drug will be given once
intravenously; on the second day, the drug will be given once orally; and
for the remainder of the (two week) inpatient period, the drug will be given
intravenously two or three times a day. The volunteer will then take the
drug by mouth two or three times a day as an outpatient. The volunteer will
be required to return to NIH once a week for monitoring for the first six
weeks as an outpatient. After that, the patient will come to clinic every
two weeks for six weeks, then every three weeks while on the study. With a
Phase I Study, everything is very much up in the air and subject to
negotiation and changes as the study progresses. At completion of the
study, patients can either be transferred to other treatment protocols if
they are eligible, or drop out, at their option.
METHODOLOGY: ddI is a Chain Terminator. ddI changes in your body to an
activated form of ddA, a "fake" version of adenosine which doesn't let
anything else chain onto it. This means that when HIV tries to replicate
itself by copying its RNA to DNA, the "fake" ddA gets added to the DNA
strand instead of real adenosine. ddA doesn't have the necessary "hooks"
for the next compound in the chain to link into. The DNA strand just stops,
halted in its tracks, incomplete and ineffective. ddI is handled by the
body differently than AZT, and it appears to be less toxic for bone-marrow
cells than AZT (in the test tube).
NOTES: Preliminary results with another form of this drug, ddA, indicated
that, at the doses tested, it could be tolerated for up to eight weeks
without major side effects (toxicity problems). Some patients on ddA had
increases in their T4 cell counts. ddA is converted in the body to ddI, and
as mentioned above, ddI is converted back again to an activated form of ddA,
so it is likely that similar therapeutic results will be obtained with ddI.
The doses that will be tested in this study are similar to the doses that
have already been tested with ddA.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drug.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328
----------------------------------------
RECOMBINANT SOLUBLE CD4
DESCRIPTION: Phase I study of the effectiveness of Recombinant Soluble CD4
in patients with AIDS/ARC.
REQUIREMENTS: This study is for people with AIDS who have had one
opportunistic infection, or symptomatic ARC patients. The study is
particularly for people WHO HAVE NOT BEEN ON AZT OR HAVE BEEN ON AZT FOR SIX
WEEKS OR LESS. Participants must be off AZT and other anti-viral therapy
for at least four weeks before the study. All participants must have a
count of less than 400 T4 cells per ml, and a positive HIV p24 antigen.
TERM: The study lasts for two and a half weeks, all of which is in-patient
at the NIH Clinical Center. The possibility exists for an extension to six
months, if the participant shows a positive response.
ADMINISTRATION: The drug will be administered by a continuous infusion
through an IV.
METHODOLOGY: The CD4 receptors on the surface of your T4 cells are the
places that HIV attaches to when it binds to and attacks your T4 cells.
Recombinant Soluble CD4 is like the attachment points without the T4 cells
underneath it. It is hoped that HIV will attach to the CD4 on the R.S. CD4
instead of on your actual T4 cells, and since R.S. CD4 is not attached to a
real T4 cell, and is thus useless to HIV (because it is not a real T4 cell,
and thus cannot be taken over and used by HIV to hide and to replicate
itself), that HIV will thus be rendered ineffective and unable to rep
licate.
NOTES: Preliminary studies revealed no apparent side effects (no toxicity
problems). There is currently a long waiting list to get onto the CD4
protocol.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drug.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328
***************************************************************************
PNEUMOCYSTIS CARINII PNEUMONIA (PCP) PROTOCOLS
----------------------------------------------------
DAPSONE OR DAPSONE/PYRIMETHAMINE FOR PCP PROPHYLAXIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity and
efficacy of weekly dapsone or dapsone/pyrimethamine in HIV-infected persons
with prior history of PCP or who have less than 250/mm^3 CD4 cells.
REQUIREMENTS: Participants must be: 18 years of age or older; HIV
positive; and able to provide informed consent. Participants must have
either a history of documented PCP that has been successfully treated or a
CD4 count of less than 250/mm^3. Participants must be at least two weeks
from other anti-PCP prophylaxis. This study is only practical for people
living within a 100 mile radius of NIH.
TERM: One year if beneficial, or stopped if the participant develops PCP or
significant toxicity while on therapy.
ADMINISTRATION: This is an outpatient study comprised of two phases. The
initial phase will consist of open dose escalation with the first five
participants receiving dapsone 100 mg orally once a week. Dose escalation
will continue in increments of 100 mg every five participants until dose-
limiting toxicity is reached in 20% of patients at a given dose. After
establishment of a tolerated dose of dapsone, pyrimethamine 25 mg will be
added. After the dose escalating phase is completed, all subsequently
entered participants will be randomized to receive either dapsone or
dapsone/ pyrimethamine. Participants will be seen in the outpatient clinic
weekly for four weeks, then every two weeks for lab work and every six weeks
for nursing visits for a period of one year.
METHODOLOGY: A study of PCP in a rat model suggests that intermittent
administration of dapsone, which is a sulfone, could prevent development of
PCP. Efficacy of dapsone appears to be enhanced by a dihydrofolate
reductase inhibitor, trimethoprim, therefore it is possible that such agents
used in combination could result in improved prevention against PCP.
Pyrimethamine is a more potent agent against PCP than trimethoprim and is
effective for a longer period in the body. Combination dapsone and
pyrimethamine therapy has the advantage of being potentially well-tolerated,
easily administered, and inexpensive.
NOTES: Possible side effects include anemia, methemoglobinemia (a condition
in which the hemoglobin has been changed by a toxic substance), decreased
white blood cells, hepatitis, rash, nausea, and fatigue.
CONTROLS: None
ORGANIZATIONS: Georgetown University Hospital: Center for HIV Disease;
National Institutes of Health: National Institute of Allergy and Infectious
Diseases (NIAID)/National Cancer Institute (NCI)/Clinical Center
CONTACTS: Georgetown University Hospital (Center for HIV Disease): Dr.
James Lavelle, Georgetown University Hospital, 3800 Reservoir Road, N.W.,
Washington, DC 20007, (202) 687-8826
National Institutes of Health: Debbie Ogata-Arakaki, Building 10, Room
10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
PIRITREXIM AND LEUCOVORIN THERAPY FOR PCP
DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance,
and efficacy of oral piritrexim and leucovorin for the initial treament of
Pneumocystis carinii pneumonia (PCP) in people with AIDS.
REQUIREMENTS: Participants must have AIDS as defined by the Centers for
Disease Control, be at least 18 years of age, and able to sign an informed
consent form. Participants must have untreated PCP (first or second
episode) documented within 36 hours of initiation of study therapy.
Laboratory values must also be within certain limits (PaO2 greater than 60
or A-A gradient less than 30, and fever, respiratory symptoms or abnormal
CXR).
TERM: 21 days of therapy with two month follow-up
ADMINISTRATION: Participants will receive oral daily doses of piritrexim
for 21 days and leucovorin for 23 days.
METHODOLOGY: Piritrexim is`a dihydrofolate reductase inhibitor that has
demonstrated the ability to block folate metabolism, essential in the growth
of Pneumocystis organisms. The use of piritrexim is complicated by its
potential for bone marrow suppression, demonstrated in initial trials of the
drug as an anti-cancer agent. Therefore, leucovorin, a pre-made folate with
the ability to rescue human cells without reversal of the anti-Pneumocystis
effects of piritrexim, will be used concurrently.
NOTES: Possible side effects include a decrease in white blood cell count
or platelet count, anemia, mouth sores, rash, and increase in liver enzymes.
CONTROLS: None
ORGANIZATION: National Institutes of Health: National Institute of Allergy
and Infectious Disases (NIAID)/National Cancer Institute (NCI)/Clinical
Center
CONTACT: Donna O'Neill, Building 10, Room 10D48, National Institutes of
Health, Bethesda, MD 20892, (301) 496-9565
***************************************************************************
CMV RETINITIS PROTOCOLS
----------------------------------------
FOSCARNET FOR CMV RETINITIS
DESCRIPTION: Study of the safety and effectiveness of foscarnet in AIDS
patients who have CMV retinitis.
REQUIREMENTS: This study is for people ages 18 to 60 with AIDS and a
positive HIV test who have CMV retinitis which is not immediately sight-
threatening. One or both eyes may be affected by the retinitis.
Participants must designate someone with a Durable Power of Attorney, and
must also satisfy certain laboratory conditions (serum creatinine less than
or equal to 2.0 mg/dl; neutrophil counts of greater than 1000/mm^3;
hemoglobin of greater than or equal to 8 g/dl; and platelets of greater than
25,000/mm^3). The following people are excluded: those who have been
treated with gan ciclovir or foscarnet for CMV retinitis in the past; those
who are currently taking acyclovir orally or intravenously; those who have a
history of intolerance to AZT; those with corneal, lens, or vitreous
opacification which precludes fundus examination, or other retinal diseases;
and people taking other investigational drugs. Women must have a negative
pregnancy test within 14 days of the start of the study, and agree to
practice contraception for the duration of the study plus three months
afterwards.
TERM: Three weeks of inpatient treatment at the NIH Clinical Center for
those receiving foscarnet, then outpatient treatment until significant
progression of the CMV retinitis is observed. Patients who complete the
study can continue receiving foscarnet from the manufacturer at no charge
until it becomes a marketed drug.
ADMINISTRATION: Patients must undergo a physical examination including
blood tests, a chest x-ray, electrocardiogram, and tests to determine the
severity of the CMV retinitis. Patients will be randomly divided into three
groups. The first group will receive foscarnet intravenously three times a
day as inpatients at NIH for three weeks, and then once a day as
outpatients. The second group will receive the same treatment as the first
group, plus oral AZT. A third group will receive only AZT. Patients in all
groups will also receive aerosolized pentamidine to lower the risk of P
neumocystis carinii pneumonia. Patients receiving foscarnet will have a
Hickman catheter inserted. This device is a plastic tube inserted in a
large central vein through which the drug is administered. This eliminates
the need to administer the drug into a peripheral vein each time. The tube
is placed during a simple surgical procedure performed under general
anesthesia.
Patients will be examined weekly to check for progression of the CMV
retinitis. If significant disease progression occurs in the patients
receiving only AZT, foscarnet will be made available to them.
Frequent blood testing is also required, up to 450 ml in a six-week period.
Urine tests will be taken once a week during the first three weeks, then
once every two weeks for the rest of the study.
METHODOLOGY: Foscarnet has been proven to inhibit viral activity in human
herpes viruses by interfering with the ability of the viruses to reproduce
themselves without significantly interfering with the ability of the rest of
the body's cells to reproduce. Foscarnet has been used as a treatment for
CMV in Europe, Canada, and the United States. Foscarnet also does not
appear to have the toxic effects on bone marrow that AZT does, thus giving
hope that people with CMV retinitis may have an effective treatment for this
disease without having to stop taking AZT. Ganciclovir (also k nown as
DHPG), the other treatment being explored for CMV retinitis, cannot be taken
at the same time as AZT. Foscarnet also has some action against HIV.
NOTES: Possible side effects of foscarnet include decreased kidney
function, confusion, inflammation of the veins, anemia, headache, fatigue,
and seizures. The Hickman catheter used for injection of the Foscarnet can
also become infected. AZT may cause decreased white blood cell counts,
making the patient more susceptible to infection, or anemia. Aerosolized
pentamidine may cause constriction of the bronchial airways.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Eye Institute/National
Institute for Allergy and Infectious Diseases
CONTACT: Barbara Baird, Building 10, Room 10D48, National Institutes of
Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
GANCICYCLOVIR (DHPG) FOR CMV RETINITIS (ACTG 071)
DESCRIPTION: Study of the effectiveness of gancicyclovir (DHPG) in patients
with AIDS who have peripheral CMV retinitis which is not immediately sight-
threatening.
REQUIREMENTS: Participants must: be at least 13 years old; have AIDS by
the CDC definition or have confirmation of HIV infection by a positive
ELISA, p24 antigen, or HIV culture; have a life expectancy of at least four
months; be able to sign an informed consent form; and have CMV retinitis
diagnosed by an ophthalmologist using indirect ophthalmoscopy, and
documented by retinal photographs. The retinitis must not be immediately
sight-threatening, i.e. retinal lesions must be greater than 1500 microns
from the edge of the optic disc, outside of the major temporal vascular
arcades, and greater than 3000 microns from the fovea.
People will be excluded who: have immediately sight-threatening retinitis;
only have retinal lesions which cannot be photographed; require continued
treatment with other medications such as antimetabolites, alkylating agents,
nucleoside analogs (except AZT as noted below under Administration); have
ocular media opacities (corneal, lenticular, or vitreal) which prevent
ophthalmologic and photographic retinal assessment; have ocular conditions
requiring immediate surgical correction, e.g. retinal tear, detachment; have
had previous treatment with anti-cytomegalovirus therapy, e.g. gan
cicyclovir, foscarnet, or CMV hyperimmune globulin; are receiving another
investigational drug other than aerosolized pentamidine; or who have
demonstrated hypersensitivity to acyclovir. Women who are pregnant, nursing
mothers, or who test positive on a pregnancy test, and men or women who are
not using adequate birth control measures are also excluded. Laboratory
tests must also be within certain limits (absolute neutrophil count greater
than or equal to 1000/mm^3; platelets count of greater than or equal to
50,000/mm^3; serum creatinine less than 1.5 mg/dl).
TERM: 16 weeks, with the option of continuing on "open-label" gancicyclovir
after the study period ends. Participants must use an effective method of
birth control during and after the conclusion of the study: 30 days for
women, 90 days for men.
ADMINISTRATION: Participants will be divided into two groups. The first
group will receive immediate gancicyclovir treatment. The second group will
receive delayed gancicyclovir treatment. While AZT is not permitted while
on the study (because both gancicyclovir and AZT cause bone marrow
suppression, and the combination can be too toxic), people in the delayed
treatment group can continue on AZT until their gancicyclovir treatment
starts. People in the delayed treatment group who show progression of their
retinitis will be eligible to start immediate gancicyclovir therapy.
Gancicyclovir is administered intravenously, usually through a Hickman or
similar catheter (which is a plastic tube in your chest which goes directly
into a vein), over the course of one hour. Gancicyclovir is given at 5
mg/kg once every twelve hours for the first two weeks, and then once a week
at 5 mg/kg for the next 14 weeks. If the participant develops severe side
effects, gancicyclovir therapy will be either at a reduced dosage,
suspended, or discontinued.
METHODOLOGY: Gancicyclovir (also known as dihydroxy-propoxymethyl guanine
or DHPG) interferes with the DNA synthesis necessary for cytomegalovirus to
reproduce.
NOTES: Participants must be referred by their physician. Side effects from
gancicyclovir range from lowered white blood cell counts, decreased platelet
counts, skin rashes, hives, nausea, vomiting, dizziness, bleeding and
bruising, irritation of the veins, and possible impairment of reproductive
or sexual function (possibly permanently). Other side effects which have
been observed include abnormalities in liver or kidney function, low blood
pressure, fainting, headache, anemia, swelling, fever, damage to nerves,
loss of hair, intestinal bleeding, seizures, loss of hearing, and p
sychological changes including confusion, irritability, nightmares,
hallucinations, or psychosis. Damage to eggs or sperm may result, which is
one of the reasons why contraception while on gancicyclovir is essential (in
addition to not passing HIV on to future offspring).
CONTROLS: None. All participants will receive gancicyclovir eventually,
but 50% of participants will receive it immediately, and 50% will receive it
on a delayed basis.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Interested people should have their doctor call Dr. David Parenti,
George Washington University, (202) 994-4716, or call Mary Beth Goldin at
(202) 994-2417 for more information.
***************************************************************************
TOXOPLASMOSIS PROTOCOLS
-------------------------------------------
PYRIMETHAMINE AND DAPSONE FOR TOXOPLASMOSIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance
and effectiveness of combination therapy with dapsone and pyrimethamine for
the treatment of central nervous system toxoplasmosis in persons with AIDS
who are resistant to or intolerant of conventional therapy.
REQUIREMENTS: Participants must: have AIDS as defined by the Centers for
Disease Control; be at least 18 years of age; be able to sign an informed
consent; and be willing to sign a durable power of attorney. Participants
must have cerebral toxoplasmosis and either have been intolerant of or
failed conventional therapy (pyrimethamine and sulfadiazine).
TERM: Life-long if therapy is beneficial. Study will be stopped if the
participant deteriorates at 14 days of therapy or fails to improve at 21
days of therapy.
ADMINISTRATION: Participants will receive oral daily doses of pyrimethamine
25 mg, dapsone 100 mg, and leucovorin 10 mg. Adjustments of pyrimethamine
and dapsone will be made if the participant fails to respond. All
participants will be admitted to the NIH Clinical Center for induction of
therapy. After seven inpatient days, participants medically stable and
reliable will be discharged to continue therapy as outpatients.
Participants will be seen in the NIH outpatient clinic weekly for the first
three weeks, and every two weeks thereafter.
METHODOLOGY: Toxoplasmosis is a life-threatening parasitic infection caused
by a protozoa, toxoplasma gondii. Pyrimethamine, a dihydrofolate reductase
inhibitor and dapsone, a sulfone agent, are known to block folic acid
metabolism, an important pathway in both humans and toxoplasma organisms.
Leucovorin, mentioned above, allows the body's cells to bypass the blockade
without affecting the anti-protozoan activity. In combination, these drugs
have the potential to be at least as effective as the conventional regimen,
pyrimethamine and sulfadiazine, but less toxic, for treatment of
toxoplasmosis.
NOTES: Possible side effects include a decrease in white blood cell count
or platelet count, anemia, methemoglobinemia, hepatitis, kidney problems,
rash, nausea, and vomiting.
CONTROLS: None
ORGANIZATION: National Institutes of Health: National Institute of Allergy
and Infectious Diseases (NIAID)/National Cancer Institute (NCI)/Clinical
Center
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-9565
***************************************************************************
MISCELLANEOUS PROTOCOLS
----------------------------------------
BLOOD DRAWING STUDY
DESCRIPTION: Blood is drawn for research on the immune response to the AIDS
virus.
REQUIREMENTS: Patients must be positive for antibodies to HIV-1, without
severe anemia. Medication usage is acceptable.
TERM: Several hours as an out-patient at the NIH Clinical Center.
ADMINISTRATION: One unit of blood is drawn, the same amount that would be
given when donating blood for transfusion.
COMPENSATION: Participants in the study will receive compensation of
$30.00.
METHODOLOGY: The blood drawn will be used in research to fight HIV.
CONTROLS: Not applicable
ORGANIZATION: National Institutes of Health/National Heart, Lung, and Blood
Institute/Pulmonary Branch, Bethesda, MD 20892
CONTACT: Pulmonary Branch, (301) 496-2449
----------------------------------------
BRONCHOALVEOLAR LAVAGE STUDY
DESCRIPTION: Study to assess the impact of HIV-1 infection on lung defense
mechanisms.
REQUIREMENTS: Patients must be between the ages of 18 and 60, be positive
for antibodies to HIV, and not had active pulmonary opportunistic infections
(e.g. Pneumocystis Carinii Pneumonia or other lung disorders) in the last
three months. Infection prior to three months, current medication use or
Kaposi's sarcoma are not exclusions.
TERM: The study involves one full day as an in-patient at the NIH Clinical
Center.
ADMINISTRATION: Participants will receive a complete medical evaluation
including a medical history, physical examination, chest X-rays,
electrocardiogram, urinalysis, blood tests, lung function studies, and
bronchoscopy with washes for analysis of cells and potential pneumonias.
COMPENSATION: Participants in the study will receive compensation of
$122.00.
METHODOLOGY: Analysis will be made of the washes of the lungs so
researchers can gather more information on what organisms attack the lungs,
and how the lungs' defense mechanisms operate.
NOTES: No prescriptions are dispensed. Results of testing are made
available to the participant and a referring physician.
CONTROLS: Not applicable
ORGANIZATION: National Institutes of Health/National Heart, Lung, and Blood
Institute/Pulmonary Branch, Bethesda, MD 20892
CONTACT: Pulmonary Branch, (301) 496-2449
----------------------------------------
BRONCHOSCOPY STUDY
DESCRIPTION: A study to determine the existance of pneumocystis in
individuals with prior history of PCP and the presence of pneumocystis,
cytomegalovirus, or other pulmonary pathogens in asymptomatic HIV-positive
individuals without past history of PCP. A secondary goal is to determine
whether conventional and experimental laboratory techniques such as
bronchoscopy and sputum induction can detect the early presence of
cytomegalovirus, and how these findings correlate with future clinical
developments.
REQUIREMENTS: Participants must: be at least 18 years of age; be able to
sign an informed consent form; have a normal chest X-ray; and show no
respiratory symptoms such as cough, fever, chest pain, or shortness of
breath.
TERM: Approximately one to two days
ADMINISTRATION: Participants will not receive any therapeutic treatment.
Participants will be screened, and if eligible undergo the following:
1. Blood tests
2. Pulmonary function test, a breathing test which is done as an
outpatient and takes approximately 15-30 minutes
3. Two induced sputum collections, where the participant breathes in a
mist for appoximately 15 minutes, and then coughs into a sterile cup
4. Bronchoscopy with biopsy, a procedure that involves placing a thin
flexible tube into your airways, washing the cells of the lining of the lung
with a salt water solution, and obtaining several small pieces of lung
tissue under X-ray guidance. This tissue is then examined under a
microscope. The procedure is done under local anesthesia and involves
admission into the hospital for one to two days.
METHODOLOGY: Pneumocystis and cytomegalovirus (CMV) are the most common
life-threatening causes of morbidity and mortality in patients with HIV
infection. Whether these organisms are present in an asymptomatic HIV-
infected cohort with varied respiratory histories, and the role various
tests play in diagnosis of these infectious pulmonary pathogens is unclear.
Of special interest is determining the importance of various diagnostic
specimens in documenting the presence of CMV pneumonitis. To date, there is
no consensus about how best to diagnose CMV pulmonary infection. Due to t
he increase in PCP prophylactic therapy, it is likely that other pathogens
such as CMV will be a greater cause of morbidity and mortality.
CONTROLS: None
ORGANIZATION: National Institutes of Health: Clinical Center/National
Institute of Allergy and Infectious Diseases (NIAID)
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
GP-160 (VACCINE)
DESCRIPTION: Experimental vaccine against HIV
REQUIREMENTS: You must be male, negative (non-reactive) on the ELISA test
for antibodies to HIV, and have had no unsafe sex for at least three months
prior to the screening. Participants cannot be promiscuous or in an unsafe
sexual relationship with a HIV-positive partner. A commitment is required
to not have sex which will place you at risk for HIV infection (either oral
or anal, with or without condoms) for at least three months following
vaccination (a year is desired).
TERM: Approximately 13 months
ADMINISTRATION: Initial screening, blood work, and a tetanus/diptheria
booster shot for people who aren't current; followed by an intensive
physical examination four weeks later; then administration of the vaccine
by intramuscular injection. Required follow-up visits once a week for four
weeks, then once a month for the next year.
METHODOLOGY: gp-160 is the protein that forms the protein coat of HIV.
This vaccination is NOT a "dead" virus, so there is zero chance of HIV
infection from the vaccine. gp-160 is synthesized using recombinant DNA
techniques (gene splicing). The hope is that your body will respond to the
protein and form antibodies to it (just like any other vaccine). One result
of this is that if the vaccine works, volunteers may then test positive for
HIV antibodies on the ELISA test. The more sophisticated Western Blot test,
done by a competent laboratory, should be able to tell the differ ence
between HIV infection and antibodies formed in response to gp-160.
Volunteers will get notarized copies of their Western Blot tests before and
after participation in the study, as well as a detailed description. Be
warned, however, that insurance companies (both health and life) may still
discriminate against you because of testing positive for HIV antibodies, and
other problems could arise with regard to employment in the military, or the
State Department, etc.
NOTES: Because the study relies on the Western Blot test to make sure that
individuals do not have HIV before the study begins, 50% of the volunteers
have been rejected after the initial screening (because of problems in
getting a clear Western Blot test). The researchers think that this may be
because the Western Blot test is too sensitive, and is reacting to non-HIV
proteins. Until something can be proved, they are rejecting anyone who does
not have a completely clear Western Blot.
CONTROLS: Very few. One fifth of the volunteers at the highest dosage
levels will get a harmless substance called KLH as a control group to see
how their immune response differs from the immune response of the volunteers
getting gp-160. But, basically, almost all of the volunteers get the actual
vaccine.
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID)
CONTACT: Margaret Easter, Building 10, Room 11B-13, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
HIV & HEART DISEASE STUDY
DESCRIPTION: Long-term study of heart disease in people who are infected
with HIV.
REQUIREMENTS: Participants must be HIV positive.
TERM: The study is expected to run until June, 1993.
ADMINISTRATION: Participants will go to the study center every four months,
and will undergo three non-invasive tests of their hearts: an EKG
(electrocardiogram), an echocardiogram, and a Signal Averaged EKG (a more
sensitive, computer-processed version of the EKG). Blood will also be drawn
for analysis. Study hours are on Tuesdays, from 8:00 a.m. to 1:00 p.m. If
abnormalities are detected, participants will be asked to return every two
months.
METHODOLOGY: The EKG and other tests help analyze the condition of your
heart. The blood work checks for antibodies to heart antigens. The two
primary heart diseases being watched for are cardiomyopathy (enlargement of
the heart), and pericardial effusions (which are fluids in the sack around
the heart).
Seventy percent of AIDS patients showed cardiac problems at autopsy, many of
these problems might have been amenable to treatment with appropriate drugs.
Monitoring can help detect these types of problems early enough that they
can be treated. Many people who aren't HIV-positive but have a history of
heart disease in their family undergo this type of monitoring as a matter of
routine.
No actual treatment is performed during this study. If problems are
detected, participants are referred to their physician for treatment. Full
cooperation and access to medical records will be provided by the
researchers.
NOTES: Participants will have their results evaluated by and be seen by a
cardiologist every time they come in for testing. Confidentiality of
patient records is maintained. Copies of all testing records are sent on
request to either the participant or the participant's physician.
CONTROLS: Not applicable
ORGANIZATION: George Washington University Hospital, Division of Cardiology
CONTACT: Sara Adams, Room 2440 North, George Washington University
Hospital, 901 23rd Street, N.W., Washington, DC 20037, (202) 994-3909
----------------------------------------
MEGACE
DESCRIPTION: This is a double-blind, controlled study of Megace (Megestrol
Acetate) in people with AIDS who have severe weight loss because of HIV.
REQUIREMENTS: Participants must have a diagnosis of AIDS according to the
CDC definition, with weight loss of at least 10% of normal body weight.
TERM: Three month study period, followed by a period in which the
participants can continue on their assigned drug, or go to "open-label"
megace where they are guaranteed to be receiving the actual drug.
Participants can go on "open-label" Megace if their weight loss continues
during study.
ADMINISTRATION: Participants will be divided into four groups: one group
will receive 800 mg/day of Megace, another group will receive 400 mg/day of
Megace; another group will receive 100 mg/day of Megace; and the fourth
group will receive a placebo. Megace is a suspension in a liquid which is
taken once per day, either before or after breakfast.
METHODOLOGY: Megace (Megestrol Acetate) is a derivative of progesterone
(one of two the female sex hormones) that has been used in the past to treat
breast cancer patients. The study is to determine the efficacy of Megace in
AIDS patients. Megace has been reported to stimulate appetite and weight
gain.
CONTROLS: Four arm, controlled study. This means that there is an 86%
chance that you will receive some level of Megace, and A 14% CHANCE THAT YOU
WILL RECEIVE A PLACEBO.
ORGANIZATION: Veterans Affairs Hospital Medical Center, in conjunction with
the Washington Hospital Center (participants do not have to be VA eligible);
also George Washington University AIDS Clinical Trials Unit.
CONTACT: Pat Kramer or John Scott, Veterans Affairs Medical Center, 50
Irving Street, N.W., Washington, DC 20422, (202) 745-8694; Mary Beth
Goldin, George Washington University AIDS Clinical Trials Unit, 2300 I
Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
***************************************************************************
OTHER PROTOCOLS
For the most up-to-date information, call the NIAID AIDS Trial Line at 1-
(800) TRIALS-A [874-2572].
Aerosolized pentamidine, long term, open-label, Georgetown University, Dr.
James Lavelle, (202) 687-8826
AZT & Acyclovir, double-blind, placebo-controlled, in mildly symptomatic
HIV+, Georgetown University, Dr. James Lavelle, (202) 687-8826
AZT & Chemotherapy for untreated HIV-related CNS lymphoma, George Washington
University, Dr. Rick Schulof, (202) 994-4200
B12/Folate for people on AZT, Georgetown University, Pamela Harding, (202)
687-7163
Neuro-psychiatric characterization of HIV+ people on AZT, Georgetown
University, Pim Brouwers, 687-4954
HIV+ with symptoms for study of physical and psychological needs, Catholic
University of America, Dr. Mary O'Brien, (301) 635-5400
Salivary Function in HIV+, National Institute of Allergy and Infectious
Diseases, Dr. Yeh, (301) 496-1478
Eye movement in asymptomatic gay men, National Institute of Allergy and
Infectious Diseases, Robert Lipman, (301) 496-6295
Eye examinations for people with AIDS and ARC, Whitman-Walker Clinic in
conjunction with Howard University, Dr. Basil Vareldzis, (202) 797-3534
Vaccine against HIV, Johns Hopkins University, Carol Hilton, (301) 955-7283
(collect)
***************************************************************************
Copyright (C) 1988,1989 by Washington HIV News, all rights reserved.
Permission is granted for non-commercial use only.phil@wubios.WUstl.EDU (J. Philip Miller) (11/20/89)
Forwarded message:
>From pyrdc!lighthouse!rock@uunet.UU.NET Tue Oct 24 19:15:38 1989
Date: Tue, 24 Oct 89 18:56:22 GMT-0500
From: pyrdc!lighthouse!rock@uunet.UU.NET (Roger Rock Rosner)
Message-Id: <8910242356.AA01258@ lighthouse >
To: phil@wubios, ddodell@stjhmc.fidonet.org
Subject: Washington HIV News: V1N3, 1/3
***************************************************************************
TREATMENT - Table of Contents August 1989 - Vol 1, No 3
Anti-retroviral protocols
Alpha Interferon and Interleukin-2
Alternating/Intermittent AZT and ddC (ACTG 047)
AS-101 and AZT
AzdU
AZT and Acyclovir (ACTG 063)
AZT and Alpha Interferon
AZT and GM-CSF
AZT and Interleukin-2
AZT for Veterans
AZT in Hemophiliacs (ACTG 036)
AZT, Alpha Interferon, and GM-CSF
Betaseron and Reduced Dose AZT
ddI (2',3'-dideoxyinosine)
Recombinant Soluble CD4
Pneumocystis carinii Pneumonia (PCP) protocols
Dapsone or Dapsone/Pyrimethamine
Piritrexim and leucovorin
CMV Retinitis protocols
Foscarnet
Gancicyclovir (ACTG 071)
Toxoplasmosis protocols
Pyrimethamine and Dapsone
Miscellaneous protocols
Blood Drawing Study
Bronchoalveolar Lavage Study
Bronchoscopy Study
gp-160 (Vaccine)
HIV & Heart Disease Study
Megace
Other protocols
***************************************************************************
ANTI-RETROVIRAL PROTOCOLS
----------------------------------
ALPHA INTERFERON AND INTERLEUKIN-2
DESCRIPTION: An evaluation of the toxicity and effectiveness of the
combination of alpha interferon and interleukin-2 in the treatment of
patients with HIV infection.
REQUIREMENTS: Participants must: have evidence of HIV demonstrated by
ELISA and Western Blot or a positive culture for HIV; have a T4 cell count
of greater than or equal to 200/mm^3; be between the ages of 18 and 60; and
not have been exposed to chemotherapy, corticosteroid therapy or
experimental therapy for six weeks prior to entry. A negative pregnancy
test is required for women of child-bearing potential. All participants
must have a primary physician involved and available to communicate with NIH
staff during the study.
TERM: As an outpatient during the time it takes to gradually increase alpha
interferon doses to a maximum level, and hold the dose at maximum for two
weeks. As an inpatient, an additional 21 days of IL-2 infusion, with
outpatient follow-up visits for the next two months.
ADMINISTRATION: Alpha interferon is self-administered by the patient by
daily injection under the skin (much the same as the method used by
diabetics). Interleukin-2 is administered by injection into the vein
continuously for 21 days. There are weekly and bimonthly blood drawings and
clinic visits during the term of the study.
METHODOLOGY: Both alpha interferon and interleukin-2 are well-tolerated as
individual drugs in HIV-infected persons. Researchers are trying to
determine whether the use of both drugs simultaneously will result in
beneficial effects not seen in either when taken as single agents, and what
the side effects are of the combination.
NOTES: Potential side effects of alpha interferon include flu-like
symptoms, a decrease in white cells, mental changes, gastrointestinal
disturbances, temporary hair loss, minor liver problems, and congestive
cardiomyopathy. Interleukin-2 has also been associated with some side
effects such as proteinuria, mild prolongation of PTT, fever, hepatitis,
rigors, increased incidence of bacterial infection, and eosinophilia. All
these effects improved or disappeared after discontinuation of the drugs.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
ALTERNATING AND INTERMITTENT DOSES OF 2',3'-DIDEOXYCYTIDINE (DDC) AND AZT IN
PATIENTS WITH AIDS AND ARC WHO ARE NOT ON AZT (ACTG 047)
DESCRIPTION: To determine if alternating AZT and ddC (first one, then the
other) or intermittent therapy (one week on, one week off) with either drug
will decrease the side effects of either drug alone, while still suppressing
HIV.
REQUIREMENTS: Two groups of patients will be admitted to the study, one
with ARC, the other with AIDS.
Patients with ARC must have the documented presence of at least one of the
following: weight loss in excess of 15 pounds or 10 percent of body weight
within 120 days of the study; temperature greater than 38.5 degrees C (about
100 degrees F) with or without night sweats, persisting for more than 14
consecutive days or more than 15 days in a 30-day interval prior to entry
into the study; diarrhea which is defined as three or more liquid stools per
day, persisting for more than 30 days prior to entry into the study without
definable cause; recurrent oral candidiasis (thrush in the mouth); hairy
leukoplakia (white bumps which appear on the tongue and in the mouth); or a
history of Herpes Zoster (Shingles).
Patients with AIDS qualify for the study if they have CDC-defined AIDS
(fulfill the Surveillance Definition of the Centers for Disease Control),
and do not require systemic maintenance chemotherapy.
All patients (ARC and AIDS), in order to qualify for the study, must also
have a consistently positive p24 antigen test (at least 70 picograms/ml,
defined by the Abbott HIV antigen test). This means the participant must
have a positive p24 antigen test seen on two occasions, each within one
month prior to entry in the study, separated by at least 72 hours, and the
last of these observations must occur within two weeks of starting the
therapy (any negative antigen test during this period will exclude the
patient from the study). All participants must also have: a positive ELISA
HIV test; the ability to care for most personal needs requiring at most
occasional assistance; attained the age of 13 years (those between 13 and 18
must have written consent by parent or legal guardian); if a woman of child-
bearing potential, must have a negative pregnancy test within 30 days of
entry in the study and use an effective method of birth control during the
study.
All participants must also have laboratory values within certain limits:
hemoglobin of at least 9.6 g/dl (patients requiring transfusions of two
units of blood more than once a month are excluded and the last transfusion
must occur before two weeks prior to entry); granulocyte count of at least
1200 cells/mm^3; platelet count of at least 100,000/mm^3; calculated
creatinine clearance greater than 50 ml/min/1.73m^2; and transaminase less
than five times the upper limit of normal.
Patients with ARC will be excluded from the ARC study group if they have an
opportunistic infection or malignancy (tumor) fulfilling the definition of
AIDS, or have neoplasms (cancerous growths) other than basal cell carcinoma
of the skin or in-situ carcinoma of the cervix.
Patients with AIDS will be excluded from the study: if they have an active
opportunistic infection and require ongoing systemic therapy and/or
prophylaxis for an AIDS-defining opportunistic infection (an exception is
the use of inhaled aerosolized pentamidine as a preventive for Pneumocystis
Carinii pneumonia); if they have symptomatic visceral Kaposi's sarcoma (KS),
progression of KS within one month prior to entry in the study or with
neoplasms other than KS, basal cell carcinoma of the skin or in-situ
carcinoma of the cervix; or if they require antineoplastic therapy.
Patients with either AIDS or ARC will be excluded if they: demonstrate
significant malabsorption (a condition in which the body does not properly
absorb nutrients or drugs); are active substance abusers; have received any
antiretrovirals within 60 days prior to entry or have received biological
modifiers or corticosteroids within 30 days prior to entry; have significant
cardiac, liver, or neurologic disease; suffer from diabetes, kidney failure,
or alcoholism or take neurotoxic drugs such as dapsone or nitrofurantoin;
have previously taken ddC; have experienced dose-limiting or transfusion-
requiring toxicity during a previous course of AZT therapy; have a history
of Idiopathic Thrombocytopenic Purpura; require prolonged acyclovir therapy;
are women who are pregnant or are breast feeding; or are unwilling to be
followed by the medical center during the study and follow-up.
ADMINISTRATION: A total of 112 patients will be divided, randomly, into
seven different treatment regimens. All medication will be given orally,
and all patients completing the study will be followed for four weeks after
completion.
The seven groups of the study are described below:
1. Weekly Alternating. AZT is administered at 200 mg every four hours for
one week, after which AZT is stopped and ddC administration begins at 0.01
mg/kg every four hours for one week, for 24 full cycles, or 48 weeks, of
therapy administered.
2. Weekly Alternating (different dose of ddC). AZT is administered at 200
mg every four hours for one week, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one week, for 24
full cycles, or 48 weeks, of therapy administered.
3. Monthly Alternating. AZT is administered at 200 mg every four hours
for one month, after which AZT is stopped and ddC administration begins at
0.01 mg/kg every four hours for one month, for six complete cycles, or 48
weeks, of therapy administered.
4. Monthly Alternating (different dose of ddC). AZT is administered at
200 mg every four hours for one month, after which AZT is stopped and ddC
administration begins at 0.03 mg/kg every four hours for one month, for six
complete cycles, or 48 weeks.
5. Intermittent AZT. AZT is administered at 200 mg every four hours for
one week, then AZT is stopped and no drug is given for one week. After a
week with no drug, AZT is again administered for a week, for 24 cycles, or
48 weeks. No ddC is given to this group.
6. Intermittent ddC. ddC is administered at 0.03 mg/kg every four hours
for one week, alternating with one week of no drug. A total of 24 cycles,
or 48 weeks, of one week on ddC and one week with no drug will take place.
No AZT will be given to this group.
7. Continuous AZT. AZT will be administered at 200 mg every four hours
for 52 consecutive weeks. No ddC will be given to this group.
TERM: 52 weeks
METHODOLOGY: Both AZT and ddC are potent inhibitors of HIV. They are Chain
Terminators, which means they interfere with the ability of HIV to
replicate. Both these drugs place the patient at risk for serious, but
different, side effects. Researchers hope to demonstrate through this study
that alternating the use of the two drugs will reduce the side effects while
maintaining the positive aspects of HIV inhibition.
CONTROLS: None
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Mary Beth Goldin, George Washington University AIDS Clinical
Trials Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202)
994-2417
----------------------------------------
AS-101 AND AZT
DESCRIPTION: Phase I open label, dose-escalation study designed to obtain
toxicity data and preliminary data on the immunologic, anti-viral and
clinical effects of AS-101 in combination with zidovudine (AZT) in patients
with HIV infection and CD4 counts less than 200/mm^3 (or 20% of
lymphocytes).
REQUIREMENTS: Participants must be: HIV infected; 18-60 years of age; able
to provide informed consent; free from active infection or illness requiring
specific therapy that could interfere with protocol; able to tolerate AZT
100 or 200 mg every four hours or have no prior history of AZT intolerance,
and have a CD4 count less than 200/mm^3 or less than 20% of circulating
lymphocytes. Those with a history of intolerance to aerosolized pentamidine
are excluded.
TERM: 12 weeks of outpatient drug therapy if currently on AZT; otherwise
six weeks of AZT followed by 12 weeks of combination therapy.
ADMINISTRATION: This is a dose escalation study with participants receiving
escalating doses of AS-101 in combination with AZT. Participants will be
enrolled sequentially in groups of five, receiving AS-101 intravenously at
doses of 3, 5, or 8 mg/M^2 three times a week and AZT 100 or 200 mg orally
every four hours depending on tolerance for 12 weeks. The drug infusions
will take 15-60 minutes depending upon dosage. Three participants from each
dose group will be treated for a minimum of four weeks before patients are
entered at the next higher dose level.
Participants not previously treated with AZT will be started at 200 mg
orally every four hours, decreased to a minimum of 100 mg every four hours
if necessary. All participants will be required to receive at least six
weeks of AZT at a minimum of 100 mg every four hours prior to starting AS-
101.
Participants will also receive aerosolized pentamidine 300 mg every four
weeks during the study period for prophylaxis against pneumocystis.
METHODOLOGY: AZT is a potent inhibitor of HIV, however it does not reverse
the immunodeficiency associated with HIV infection, and progressive disease
frequently occurs. AS-101, a synthetic compound, has been found in vitro to
increase the response to and production of interleukin-2, a lymphokine with
immune-modulating properties. Thus, a combined regimen of AZT with AS-101
may provide some anti-retroviral and immunomodulatory activity.
NOTES: Possible side effects of AZT include nausea, headache, anemia,
decrease in white cells, and myopathy. AS-101 can cause lightening and
thinning of hair, garlic body odor, rash, nausea, headache, and
abnormalities of the urine.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
AZDU
DESCRIPTION: Phase I/II study of 3'-Azido-2',3'-dideoxyuridine (AzdU) in
people with HIV infection.
REQUIREMENTS: Participants in this study must be positive on the ELISA and
the Western Blot, and have a CD4 (T4) count between 200 and 400/mm^3.
Participants must be over age 18, have no previous use of AZT, have good
veins, and be willing to come to NIH for weekly blood drawing and clinic
visits. Participants must also have a private physician involved in their
care and available for communication with the NIH doctors and nurses during
the time they are on this study.
TERM: 14 1/2 weeks, with participants who show a beneficial response having
the option to continue treatment after the study period ends.
ADMINISTRATION: Participants will be divided into one of five groups who
will receive different dosages of AzdU. The first dose will be given
intravenously over one hour at the Clinical Center at NIH, with frequent
blood drawing to measure drug levels. Two days later, a single oral dose
will be given to measure oral absorption. Two weeks later, a twelve week
period of oral dosing of the drug will begin. There will be frequent
sampling of blood and urine during the course of the study for monitoring
and evaluation to minimize potential toxicities. Participants will be
assessed monthly for three months, and then every three months after being
on the drug for nine months.
METHODOLOGY: AzdU is a Chain Terminator, a "nucleoside analog" similar to
AZT. It works by interfering with the ability of HIV to replicate.
NOTES: AzdU has not been given to humans before, so potential side effects
are unknown. Animal studies have shown toxicities only at extraordinarily
large doses. Other nucleoside analogues have caused elevations of liver
function tests, nausea, headache, and bone marrow suppression. A total of
15 people will be enrolled in this study.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID), Laboratory of Immunoregulation
CONTACT: Dianne Lee, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
AZT AND ACYCLOVIR (ACTG 063)
DESCRIPTION: A double-blind phase II/III study of different dosages of AZT
and acyclovir in patients with AIDS.
REQUIREMENTS: Participants must have been diagnosed with AIDS within the
past four months, as defined by CDC category IV-C-1, i.e. with PCP,
cryptosporidiosis, toxoplasmosis, extraintestinal strongyloidiasis,
isosporiasis, candidiasis (esophageal, bronchial, or pulmonary),
cryptococcosis, histoplasmosis, mycobacterial infection, cytomegalovirus,
mucocutaneous or disseminated herpes simplex virus, or progressive
multifocal leukoencephalopathy. Participants must also: be positive on the
ELISA and the Western Blot; be greater than 13 years of age; and be able to
take care of themse lves requiring only occasional assistance. Women of
childbearing potential must have a negative pregnancy test within 30 days of
the start of the study and be willing to practice a barrier method of
contraception while on the study. Laboratory tests must also be within
certain limits (total neutrophil count greater than 1000/mm^3; platelet
count greater than 50,000 cells/mm^3; hemoglobin greater than 9.0 mg/dl, and
the patient cannot be transfusion dependent--the last transfusion must be at
least two weeks prior to the study; serum creatinine less than 1.5 times the
upper limit of no rmal or clearance greater than 50 ml/min; SGOT less than
five times the upper range of normal).
People will be excluded who: have symptomatic visceral or progressive
Kaposi's sarcoma (defined by more than 10 new lesions in the 30 days prior
to the study); have neoplasms other than basal cell carcinoma of the skin;
are pregnant women, nursing mothers, or women not employing birth control or
abstinence; have malabsorption as defined by persistent diarrhea greater
than six stools/day for more than four weeks; require acyclovir prophylaxis
or frequent (more than once a month) courses of acyclovir therapy for herpes
simplex virus infection, however episodic treatment with acyclovir is
permitted; have received systemic acyclovir therapy within 14 days of the
start of the study; have been previously treated with AZT for more than 120
days; have received other anti-retrovirals within 30 days of study entry;
have received ribavirin within 60 days of study entry; have received
cytotoxic chemotherapy or radiation therapy for KS within 30 days of study
entry; are participating in a protocol which compares AZT to a placebo (e.g.
ACTG 016 and ACTG 019); or are active substance abusers (methadone
maintenance therapy is permitted).
TERM: Two years
ADMINISTRATION: Participants will be divided into four groups: the first
group will get 1000 mg/day of AZT and no acyclovir; the second will get 500
mg/day of AZT and no acyclovir; the third will get 1000 mg/day of AZT and
4000 mg/day of acyclovir; and the fourth will get 500 mg/day of AZT and 4000
mg/day of acyclovir. All medication will be taken orally, every four hours
while awake (five times a day). Participants will have to come in once
every two weeks for a clinic visit. If participants demonstrate significant
toxicity, the dosage may be modified, or the therapy stopped.
METHODOLOGY: There has been some conjecture that Human Herpes Virus Six
(HHV-6) may activate HIV. Since acyclovir is an effective drug against the
whole Herpes family of viruses, it is hoped that the combination of AZT,
which has been shown to inhibit HIV replication, with acyclovir may have a
greater effectiveness with fewer side effects than either drug taken alone.
It may also allow for a lower dose of AZT while still being effective
against HIV. The negative side effects of AZT have been shown to be dose-
related, so the combination therapy of AZT and acyclovir may allow eff
ective treatment with fewer side effects (primarily bone marrow suppression)
from AZT.
NOTES: Possible side effects include lowered white blood cell count,
anemia, headache, mild confusion, fatigue, anxiety, nausea, skin rashes,
dizziness, and muscle pain. Acyclovir has some of the same side effects as
AZT, and also anorexia (loss of appetite).
CONTROLS: None. All participants are guaranteed to receive some dosage
level of AZT, and half the participants will receive some dosage level of
acyclovir.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Kathryn Grabowy, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
----------------------------------------
AZT AND ALPHA INTERFERON
DESCRIPTION: Study of AZT alone vs. AZT and Alpha Interferon vs. Alpha
Interferon alone, for people in the early stages of HIV infection.
REQUIREMENTS: Positive lymphocyte culture for HIV, or positive p24 antigen
test, or positive PCR test, and T4 cell counts of more than 500 per cubic
millimeter. Participants must be over age 18, have not participated
previously in any other HIV protocols, have good veins, and be willing to
come to NIH for weekly to biweekly blood drawing and clinic visits.
Participants may have been on AZT before. Participants must also have a
private physician involved in their care and available for communication
with the NIH doctors and nurses during the time they are on this study.
TERM: Indefinite. The study continues until the participant develops an
opportunistic infection, their T4 cell counts drop below 200, or the
participant develops severe side-effects or reactions (toxicity) to either
of the medications.
ADMINISTRATION: Participants will be divided into three groups: one will
receive AZT alone, one will receive AZT and alpha interferon, and the last
will receive alpha interferon alone. AZT is given orally; alpha interferon
is given by injection. Persons enrolled in the study will be taught to give
the alpha interferon to themselves. The AZT-only group will take 200 mg
every four hours. The AZT/alpha interferon group will take 100 mg of AZT
every 4 hours and 1 million units of alpha interferon every day. The alpha
interferon-only group will initially receive 5 million units e very day.
The doses of alpha interferon will be increased, as tolerated, to a maximum
of 35 million units per day.
METHODOLOGY: AZT is a "nucleoside analog" (a fake version of the base
thymidine) which interferes with the ability of HIV to make copies of
itself. Alpha Interferon interferes with the final assembly process of HIV
which happens as HIV tries to bud off new copies of itself into the
bloodstream.
NOTES: Potential side effects of AZT include nausea, headaches, fatigue,
and anemia that may require blood transfusion. Alpha interferon can cause
flu-like symptoms (fevers, fatigue, muscle aches, decrease in appetite), a
decrease in white blood cell count, and mental changes, including
depression, memory loss, and difficulty concentrating.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID), Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
AZT AND GM-CSF
DESCRIPTION: Phase I study of AZT (Azidothymidine) combined with GM-CSF
(Granulocyte/Macrophage-Colony Stimulating Factor) in patients with AIDS or
symptomatic HIV infection.
REQUIREMENTS: All participants must be at least 18 years old and have T4
cell counts of less than 200. Participants must have either never taken
AZT, or have taken at least 600 mg a day, and discontinued because of
toxicity to the patient's white blood cells. Participants who were on AZT
must be off it for at least four weeks prior to the study. All participants
must have a white blood cell count of less than 3,000 per cubic millimeter
and hemoglobin of greater than nine grams per deciliter. All participants
must have greater than 75,000 platelets per cubic millimeter and no t
ransfusions within the past month. People with active opportunistic
infections are excluded from the study. No other cytotoxic or
antiretrovirals may be taken while participants are in the protocol,
although prophalaxis for PCP with either Fanzidar, Bactrim, or aerosolized
Pentamidine is permitted. Women of child-bearing potential must have a
negative pregnancy test prior to the start of the study, and be willing to
use birth control measures during and for two months after the study.
TERM: 12 months, with the possibility of an extension if the patient
responds favorably to the treatment. All treatment is on an outpatient
basis from the NIH Clinical Center.
ADMINISTRATION: The AZT is given orally every four hours; the GM-CSF is
given two times a day by a self-administered injection just under the skin
(similar to the way insulin is self-injected by diabetics).
METHODOLOGY: AZT, while effective at suppressing the reproduction of HIV,
has an unfortunate side effect of suppressing the production of granulocytes
and macrophages, which are types of white blood cells, within the bone
marrow. GM-CSF stimulates the production of granulocytes and macrophages,
so it is hoped that by taking GM-CSF in combination with AZT, AZT's toxic
side effects can be reduced or eliminated, or that a larger dose of AZT with
tolerable side effects will be possible.
NOTES: If the patient's white cell counts fall while he/she is in the
study, the dosage of GM-CSF will be increased (two increases only) to try to
counter the toxicity problems.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drugs.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. James Pluda, Building 10, Room 13N248, National institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-8398
----------------------------------------
AZT AND INTERLEUKIN-2
DESCRIPTION: The study will evaluate the effectiveness and toxicity of the
combination of AZT (also known as zidovudine and Retrovir) and Interleukin-2
(IL-2) in the treatment of persons with HIV infection.
REQUIREMENTS: To be eligible to participate in the study, a person must
have HIV diagnosed by ELISA and Western Blot or a positive culture. The
person must not have had any of the opportunistic infections associated with
AIDS and must have over 200 T4 cells per cubic millimeter. If the person is
receiving AZT, he/she must be able to tolerate 200 mg every four hours.
TERM: Seventeen weeks (with possible extension of therapy if significant
improvement occurs).
ADMINISTRATION: AZT alone will be given for six weeks (orally). Following
that, AZT and IL-2 will be administered for three weeks. The IL-2 will be
administered IV continuously for three weeks and this part of the study will
be done on an inpatient basis. In addition there will be weekly or biweekly
blood drawing for the duration of the study.
METHODOLOGY: Studies have demonstrated that AZT can decrease the frequency
of opportunistic infections, but it sometimes results in bone marrow
suppression. IL-2 is a drug which stimulates the immune system.
Researchers are trying to determine whether the IL-2 might reduce the side
effects of AZT, thus allowing more patients to take full doses of AZT.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases
CONTACT: Dianne Lee, Building 10, 11th floor clinic, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
AZT FOR VETERANS
DESCRIPTION: Study of the effectiveness of AZT in a double-blind,
controlled study of patients with ARC (AIDS Related Complex).
REQUIREMENTS: Participants in the study must be VA eligible. They must be
HIV antibody positive, with T-cell counts between 200 and 500, and they must
have some minor symptoms.
TERM: The protocol lasts for three years.
ADMINISTRATION: The study drug is taken orally in 250 mg doses every four
hours, around the clock.
METHODOLOGY: AZT is a Chain Terminator, which means it interferes with the
ability of HIV to replicate. This study attempts to determine to what
extent AZT helps people with ARC.
CONTROLS: This is a double-blind, randomized, controlled study. This means
that 50% of the participants will get AZT, and THERE IS A 50% CHANCE THAT
THEY WILL NOT. No one (neither the researchers nor the patient) will know
who is or who is not on AZT.
ORGANIZATION: Veterans Affairs Medical Center
CONTACT: Pat Kramer or John Scott, Veterans Affairs Medical Center, 50
Irving Street, N.W., Washington, DC 20422, (202) 745-8694
----------------------------------------
AZT IN HEMOPHILIACS (ACTG 036)
DESCRIPTION: This is a double-blind placebo-controlled study to determine
whether AZT (also known as zidovudine or Retrovir) will delay or alter the
progression of disease in HIV infected hemophiliacs.
REQUIREMENTS: Participants must: have HIV infection confirmed by Western
Blot; be at least 12 years old; and have been diagnosed with hemophilia, Von
Willebrand's Disease, or other coagulation-deficient disorders.
Participants must have laboratory results within certain limits:
granulocyte count of at least 1000 cells/mm^3; platelet count of a least
75,000/mm^3; hematocrit greater than 30 percent; creatinine less than or
equal to 1.5 times normal or clearance of at least 50 ml/min; and
transaminases less than or equal to five times the upper limit of normal.
Participants must al so have a Karnofsky performance status of 90 (able to
carry on normal activity; minor signs or symptoms or disease), although if
this measure is impaired by hemophilia complications, a status as low as 60
will be accepted (requires occasional assistance but is able to care for
most of his/her needs).
Patients will be excluded from the study if there is a history of AIDS
defining infection or malignancy or an unexplained temperature higher than
38oC (about 100.5oF) for more than five consecutive days or on more than 10
days in any 30-day period in the two years before entering the study.
Additional exclusions are: unexplained severe diarrhea; unintentional
weight loss of more than 10 percent of body weight in the past two years;
oral hairy leukoplakia (white spots or patches on the tongue or cheek); a
history of oral candidiasis not related to antibiotics; or herpes zoster
infec tion within the past two years. People will also be excluded if:
they have taken antiretroviral agents (like AZT) within the last eight weeks
or immunomodulating drugs (like steroids); they have taken other
experimental therapy within three months; or if they require therapy with
isoniazid or rifampin. All participants will be required to practice
effective contraception, and pregnancy is a basis for exclusion from the
study.
TERM: Up to three years
ADMINISTRATION: Participants will take orally three 100 mg capsules every
four hours for five doses per day. Half of these persons will be receiving
AZT, the other half will be receiving a harmless placebo.
METHODOLOGY: AZT acts on HIV to inhibit its replication (reproduction or
copy of itself). It is a Chain Terminator.
CONTROLS: This is a double-blind, placebo-controlled study, which means 50%
of the patients will get AZT, and 50% WILL GET NONE. Neither the patient
nor the researchers will know which is which during the course of the study.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Stacy Russell, George Washington University Hematology/Oncology
Clinic, 2150 Pennsylvania Avenue, N.W., Washington, DC 20037, (202) 994-
4200
----------------------------------------
AZT, ALPHA INTERFERON, AND GM-CSF
DESCRIPTION: This study is designed to evaluate the safety and
effectiveness of giving recombinant granulocyte-macrophage colony
stimulating factor (GM-CSF) in combination with AZT and alpha interferon in
patients with HIV infection.
REQUIREMENTS: Participants must: be over age 18; have a CD4 count of 200
to 500 per cubic millimeter; be positive for HIV on both the ELISA and the
Western Blot; have good veins; and be under the care of a physician with
whom the researchers can communicate while they are on the study. People
with active opportunistic infections are excluded.
TERM: Sixteen weeks after the dosages have stabilized, all of which is
outpatient.
ADMINISTRATION: Newly enrolled patients will be divided into two groups.
One group will receive 100 mg of AZT orally every four hours for four weeks,
and then will begin on interferon with 10 million units/day by injection
under the skin with the dose escalating by five million units/day every two
weeks. When the granulocyte count falls below 1000/mm^3, GM-CSF will be
started at a dose of one microgram (ug) per kilogram of body weight per day
(ug/kg/day), by injection under the skin. The GM-CSF dose will be escalated
to maintain the granulocyte count over 1500/mm^3. Once the patient's
granulocyte count is stable on AZT, interferon, and GM-CSF, the patient will
be treated for 16 weeks. The second group is identical to the first, except
their starting AZT dose will be 200 mg every four hours. Enrollment will be
done sequentially--the first 10 patients will be in the first group, and the
second 10 will be in the second group.
NIH patients who have previously been on combination AZT/interferon therapy
will comprise a third group. Patients in this group will begin on AZT and
interferon at the doses at which they became granulocytopenic (low counts of
granulocytes) in the past, with GM-CSF at one mg/kg/day starting at the same
time. Doses of AZT, interferon, and GM-CSF will be escalated, as tolerated,
in an attempt to bring the patients up to an optimal dosing level of AZT 200
mg every four hours and interferon 10 million units per day. The treatment
period for the third group, once the patient's granulocyte count is
stabilized above 1500/mm^3, will also be 16 weeks.
METHODOLOGY: While studies in the laboratory and in humans have shown that
AZT and alpha interferon given together can inhibit HIV, up to 50% of
patients taking this combination of drugs develop granulocytopenia, a
potentially serious decrease in a particular infection-fighting white blood
cell known as the granulocyte. Granulocyte-macrophage colony stimulating
factor is a bone marrow growth factor that stimulates production of several
types of cells found in blood, including the granulocyte.
NOTES: Potential side effects of AZT include nausea, headaches, and anemia
that may require blood transfusion. Interferon can cause flu-like symptoms
(fevers, fatigue, muscle aches, decrease in appetite), a decrease in white
blood cell count, and mental changes, including depression, memory loss, and
difficulty concentrating. The combination of AZT and interferon has been
known to cause a decrease in granulocytes and depression of liver function.
GM-CSF can cause fever, bone pain, and flu-like symptoms in some patients.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases, Laboratory of Immunoregulation
CONTACT: Victoria Davey, Building 10, Room 11B09, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
BETASERON (BERA INTERFERON) AND REDUCED DOSE AZT IN AIDS AND ADVANCED ARC
PATIENTS
DESCRIPTION: Comparative study of high dose Betaseron, low dose Betaseron,
or placebo in combination with reduced dose AZT.
REQUIREMENTS: Patients must have: laboratory evidence of HIV infection;
either AIDS by CDC criteria or documentation of an absolute T4 count less
than 200; a reaction to AZT that requires dose reduction of AZT to 500-600
mg of AZT daily and the ability to tolerate this reduced dose; Karnofsky
status of 60 or greater (be able to take care of daily needs requiring only
occasional assistance); acceptable renal (kidney) function; acceptable
hepatic (liver) function; attained at least age 18; be available for follow-
up; and be willing to continue on reduced dose AZT at own expense.
Participants must have laboratory results within certain limits:
granulocyte count currently greater than 1000/mm^3; hemoglobin greater than
8.5 mg/dl; and platelet count greater than 50,000/mm^3. People will be
excluded if they have: ineffectively controlled opportunistic infections;
Kaposi's sarcoma requiring systemic chemotherapy; cytotoxic chemotherapy
within 30 days of the first Betaseron dose; proteinuria of 2+ or greater;
concurrent therapy with anti-virals other than AZT or Betaseron; chronic
concurrent therapy with acyclovir; prior therapy with interferon; HIV
encephalopathy (dementia); HIV wasting syndrome; pregnancy or lactation
(women with childbearing potential must take adequate precautions to prevent
pregnancy during treatment); active drug or alcohol abuse; New York heart
classification III or IV; uncontrolled angina pectoris (severe pain about
the heart, usually travelling down the left arm); or evidence of clinically
significant multifocal uncontrolled cardiac dysrhythmias.
TERM: Indefinite. The study will continue until the superiority of the
treatment is clearly demonstrated or disproved.
ADMINISTRATION: All patients continue on reduced dose AZT. Each patient is
assigned to one of three treatment groups--high dose Betaseron, low dose
Betaseron, or placebo. The patient administers daily injections of the
study drug into the skin (in the same way that diabetics inject themselves).
The patient must visit the test site for lab and physical evaluations once a
week for a month, biweekly for two months, and monthly thereafter.
METHODOLOGY: Many patients on AZT develop side effects which involve the
blood and must, therefore, be put on a reduced dose of AZT. In the
laboratory, Betaseron (a recombinant form of interferon Beta) has been shown
to enhance the action of AZT in blocking the ability of the HIV to make
copies of itself, to kill lymphocytes, and to spread between lymphocytes.
In clinical studies, patients who have taken Betaseron have shown evidence
of suppression of the HIV copying mechanism and a low incidence of
opportunistic infections. Although there may be side effects from
Betaseron, they are seldom related to the blood. As a result, researchers
believe that a level of AZT which is not toxic to the patient might be
combined with Betaseron to get positive results similar to a higher AZT dose
without the negative side effects of AZT on the blood.
NOTES: Possible side effects of Betaseron include mild flu-like symptoms
and redness at the injection site. These effects generally decrease and
disappear with continuing treatment. Sometimes a mild depression in blood
cell counts occurs.
CONTROLS: Two out of three patients will be given Betaseron, with the third
patient on a placebo. Although the study is placebo controlled, it should
be noted that all patients will be maintained on low doses of AZT, thus
ensuring that all patients will be receiving at least some anti-viral
therapy.
ORGANIZATION: George Washington University Hospital
CONTACT: Grace Gianturco, George Washington University AIDS Clinical Trials
Unit, 2300 I Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
----------------------------------------
DDI (2',3'-DIDEOXYINOSINE)
DESCRIPTION: Phase I Study of drug to fight HIV.
REQUIREMENTS: This study is for people with AIDS or severe ARC,
PARTICULARLY PEOPLE WHO HAVE NOT BEEN ON AZT OR HAVE BEEN ON AZT FOR SIX
WEEKS OR LESS. Participants must be off AZT and other anti-viral therapy
for at least four weeks before the study. All participants must have a
count of less than 350 T4 cells per ml, and must not be anemic or have a low
white blood count. ARC patients must have either oral thrush or weight
loss. People with severe Kaposi's sarcoma or active opportunistic
infections are excluded.
TERM: The initial phase lasts for a total of 13 months; two weeks as an
inpatient and 12 1/2 months as an outpatient. If the initial results prove
favorable, it is possible that permission will be obtained from the FDA to
continue the study for a longer period of time.
ADMINISTRATION: On the first day, the drug will be given once
intravenously; on the second day, the drug will be given once orally; and
for the remainder of the (two week) inpatient period, the drug will be given
intravenously two or three times a day. The volunteer will then take the
drug by mouth two or three times a day as an outpatient. The volunteer will
be required to return to NIH once a week for monitoring for the first six
weeks as an outpatient. After that, the patient will come to clinic every
two weeks for six weeks, then every three weeks while on the study. With a
Phase I Study, everything is very much up in the air and subject to
negotiation and changes as the study progresses. At completion of the
study, patients can either be transferred to other treatment protocols if
they are eligible, or drop out, at their option.
METHODOLOGY: ddI is a Chain Terminator. ddI changes in your body to an
activated form of ddA, a "fake" version of adenosine which doesn't let
anything else chain onto it. This means that when HIV tries to replicate
itself by copying its RNA to DNA, the "fake" ddA gets added to the DNA
strand instead of real adenosine. ddA doesn't have the necessary "hooks"
for the next compound in the chain to link into. The DNA strand just stops,
halted in its tracks, incomplete and ineffective. ddI is handled by the
body differently than AZT, and it appears to be less toxic for bone-marrow
cells than AZT (in the test tube).
NOTES: Preliminary results with another form of this drug, ddA, indicated
that, at the doses tested, it could be tolerated for up to eight weeks
without major side effects (toxicity problems). Some patients on ddA had
increases in their T4 cell counts. ddA is converted in the body to ddI, and
as mentioned above, ddI is converted back again to an activated form of ddA,
so it is likely that similar therapeutic results will be obtained with ddI.
The doses that will be tested in this study are similar to the doses that
have already been tested with ddA.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drug.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328
----------------------------------------
RECOMBINANT SOLUBLE CD4
DESCRIPTION: Phase I study of the effectiveness of Recombinant Soluble CD4
in patients with AIDS/ARC.
REQUIREMENTS: This study is for people with AIDS who have had one
opportunistic infection, or symptomatic ARC patients. The study is
particularly for people WHO HAVE NOT BEEN ON AZT OR HAVE BEEN ON AZT FOR SIX
WEEKS OR LESS. Participants must be off AZT and other anti-viral therapy
for at least four weeks before the study. All participants must have a
count of less than 400 T4 cells per ml, and a positive HIV p24 antigen.
TERM: The study lasts for two and a half weeks, all of which is in-patient
at the NIH Clinical Center. The possibility exists for an extension to six
months, if the participant shows a positive response.
ADMINISTRATION: The drug will be administered by a continuous infusion
through an IV.
METHODOLOGY: The CD4 receptors on the surface of your T4 cells are the
places that HIV attaches to when it binds to and attacks your T4 cells.
Recombinant Soluble CD4 is like the attachment points without the T4 cells
underneath it. It is hoped that HIV will attach to the CD4 on the R.S. CD4
instead of on your actual T4 cells, and since R.S. CD4 is not attached to a
real T4 cell, and is thus useless to HIV (because it is not a real T4 cell,
and thus cannot be taken over and used by HIV to hide and to replicate
itself), that HIV will thus be rendered ineffective and unable to rep
licate.
NOTES: Preliminary studies revealed no apparent side effects (no toxicity
problems). There is currently a long waiting list to get onto the CD4
protocol.
CONTROLS: None. (In a Phase I study, all patients receive the actual
drug.)
ORGANIZATION: National Institutes of Health/National Cancer Institute
CONTACT: Dr. Robert Yarchoan, Building 10, Room 12N214, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-0328
***************************************************************************
PNEUMOCYSTIS CARINII PNEUMONIA (PCP) PROTOCOLS
----------------------------------------------------
DAPSONE OR DAPSONE/PYRIMETHAMINE FOR PCP PROPHYLAXIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity and
efficacy of weekly dapsone or dapsone/pyrimethamine in HIV-infected persons
with prior history of PCP or who have less than 250/mm^3 CD4 cells.
REQUIREMENTS: Participants must be: 18 years of age or older; HIV
positive; and able to provide informed consent. Participants must have
either a history of documented PCP that has been successfully treated or a
CD4 count of less than 250/mm^3. Participants must be at least two weeks
from other anti-PCP prophylaxis. This study is only practical for people
living within a 100 mile radius of NIH.
TERM: One year if beneficial, or stopped if the participant develops PCP or
significant toxicity while on therapy.
ADMINISTRATION: This is an outpatient study comprised of two phases. The
initial phase will consist of open dose escalation with the first five
participants receiving dapsone 100 mg orally once a week. Dose escalation
will continue in increments of 100 mg every five participants until dose-
limiting toxicity is reached in 20% of patients at a given dose. After
establishment of a tolerated dose of dapsone, pyrimethamine 25 mg will be
added. After the dose escalating phase is completed, all subsequently
entered participants will be randomized to receive either dapsone or
dapsone/ pyrimethamine. Participants will be seen in the outpatient clinic
weekly for four weeks, then every two weeks for lab work and every six weeks
for nursing visits for a period of one year.
METHODOLOGY: A study of PCP in a rat model suggests that intermittent
administration of dapsone, which is a sulfone, could prevent development of
PCP. Efficacy of dapsone appears to be enhanced by a dihydrofolate
reductase inhibitor, trimethoprim, therefore it is possible that such agents
used in combination could result in improved prevention against PCP.
Pyrimethamine is a more potent agent against PCP than trimethoprim and is
effective for a longer period in the body. Combination dapsone and
pyrimethamine therapy has the advantage of being potentially well-tolerated,
easily administered, and inexpensive.
NOTES: Possible side effects include anemia, methemoglobinemia (a condition
in which the hemoglobin has been changed by a toxic substance), decreased
white blood cells, hepatitis, rash, nausea, and fatigue.
CONTROLS: None
ORGANIZATIONS: Georgetown University Hospital: Center for HIV Disease;
National Institutes of Health: National Institute of Allergy and Infectious
Diseases (NIAID)/National Cancer Institute (NCI)/Clinical Center
CONTACTS: Georgetown University Hospital (Center for HIV Disease): Dr.
James Lavelle, Georgetown University Hospital, 3800 Reservoir Road, N.W.,
Washington, DC 20007, (202) 687-8826
National Institutes of Health: Debbie Ogata-Arakaki, Building 10, Room
10D48, National Institutes of Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
PIRITREXIM AND LEUCOVORIN THERAPY FOR PCP
DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance,
and efficacy of oral piritrexim and leucovorin for the initial treament of
Pneumocystis carinii pneumonia (PCP) in people with AIDS.
REQUIREMENTS: Participants must have AIDS as defined by the Centers for
Disease Control, be at least 18 years of age, and able to sign an informed
consent form. Participants must have untreated PCP (first or second
episode) documented within 36 hours of initiation of study therapy.
Laboratory values must also be within certain limits (PaO2 greater than 60
or A-A gradient less than 30, and fever, respiratory symptoms or abnormal
CXR).
TERM: 21 days of therapy with two month follow-up
ADMINISTRATION: Participants will receive oral daily doses of piritrexim
for 21 days and leucovorin for 23 days.
METHODOLOGY: Piritrexim is`a dihydrofolate reductase inhibitor that has
demonstrated the ability to block folate metabolism, essential in the growth
of Pneumocystis organisms. The use of piritrexim is complicated by its
potential for bone marrow suppression, demonstrated in initial trials of the
drug as an anti-cancer agent. Therefore, leucovorin, a pre-made folate with
the ability to rescue human cells without reversal of the anti-Pneumocystis
effects of piritrexim, will be used concurrently.
NOTES: Possible side effects include a decrease in white blood cell count
or platelet count, anemia, mouth sores, rash, and increase in liver enzymes.
CONTROLS: None
ORGANIZATION: National Institutes of Health: National Institute of Allergy
and Infectious Disases (NIAID)/National Cancer Institute (NCI)/Clinical
Center
CONTACT: Donna O'Neill, Building 10, Room 10D48, National Institutes of
Health, Bethesda, MD 20892, (301) 496-9565
***************************************************************************
CMV RETINITIS PROTOCOLS
----------------------------------------
FOSCARNET FOR CMV RETINITIS
DESCRIPTION: Study of the safety and effectiveness of foscarnet in AIDS
patients who have CMV retinitis.
REQUIREMENTS: This study is for people ages 18 to 60 with AIDS and a
positive HIV test who have CMV retinitis which is not immediately sight-
threatening. One or both eyes may be affected by the retinitis.
Participants must designate someone with a Durable Power of Attorney, and
must also satisfy certain laboratory conditions (serum creatinine less than
or equal to 2.0 mg/dl; neutrophil counts of greater than 1000/mm^3;
hemoglobin of greater than or equal to 8 g/dl; and platelets of greater than
25,000/mm^3). The following people are excluded: those who have been
treated with gan ciclovir or foscarnet for CMV retinitis in the past; those
who are currently taking acyclovir orally or intravenously; those who have a
history of intolerance to AZT; those with corneal, lens, or vitreous
opacification which precludes fundus examination, or other retinal diseases;
and people taking other investigational drugs. Women must have a negative
pregnancy test within 14 days of the start of the study, and agree to
practice contraception for the duration of the study plus three months
afterwards.
TERM: Three weeks of inpatient treatment at the NIH Clinical Center for
those receiving foscarnet, then outpatient treatment until significant
progression of the CMV retinitis is observed. Patients who complete the
study can continue receiving foscarnet from the manufacturer at no charge
until it becomes a marketed drug.
ADMINISTRATION: Patients must undergo a physical examination including
blood tests, a chest x-ray, electrocardiogram, and tests to determine the
severity of the CMV retinitis. Patients will be randomly divided into three
groups. The first group will receive foscarnet intravenously three times a
day as inpatients at NIH for three weeks, and then once a day as
outpatients. The second group will receive the same treatment as the first
group, plus oral AZT. A third group will receive only AZT. Patients in all
groups will also receive aerosolized pentamidine to lower the risk of P
neumocystis carinii pneumonia. Patients receiving foscarnet will have a
Hickman catheter inserted. This device is a plastic tube inserted in a
large central vein through which the drug is administered. This eliminates
the need to administer the drug into a peripheral vein each time. The tube
is placed during a simple surgical procedure performed under general
anesthesia.
Patients will be examined weekly to check for progression of the CMV
retinitis. If significant disease progression occurs in the patients
receiving only AZT, foscarnet will be made available to them.
Frequent blood testing is also required, up to 450 ml in a six-week period.
Urine tests will be taken once a week during the first three weeks, then
once every two weeks for the rest of the study.
METHODOLOGY: Foscarnet has been proven to inhibit viral activity in human
herpes viruses by interfering with the ability of the viruses to reproduce
themselves without significantly interfering with the ability of the rest of
the body's cells to reproduce. Foscarnet has been used as a treatment for
CMV in Europe, Canada, and the United States. Foscarnet also does not
appear to have the toxic effects on bone marrow that AZT does, thus giving
hope that people with CMV retinitis may have an effective treatment for this
disease without having to stop taking AZT. Ganciclovir (also k nown as
DHPG), the other treatment being explored for CMV retinitis, cannot be taken
at the same time as AZT. Foscarnet also has some action against HIV.
NOTES: Possible side effects of foscarnet include decreased kidney
function, confusion, inflammation of the veins, anemia, headache, fatigue,
and seizures. The Hickman catheter used for injection of the Foscarnet can
also become infected. AZT may cause decreased white blood cell counts,
making the patient more susceptible to infection, or anemia. Aerosolized
pentamidine may cause constriction of the bronchial airways.
CONTROLS: None
ORGANIZATION: National Institutes of Health/National Eye Institute/National
Institute for Allergy and Infectious Diseases
CONTACT: Barbara Baird, Building 10, Room 10D48, National Institutes of
Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
GANCICYCLOVIR (DHPG) FOR CMV RETINITIS (ACTG 071)
DESCRIPTION: Study of the effectiveness of gancicyclovir (DHPG) in patients
with AIDS who have peripheral CMV retinitis which is not immediately sight-
threatening.
REQUIREMENTS: Participants must: be at least 13 years old; have AIDS by
the CDC definition or have confirmation of HIV infection by a positive
ELISA, p24 antigen, or HIV culture; have a life expectancy of at least four
months; be able to sign an informed consent form; and have CMV retinitis
diagnosed by an ophthalmologist using indirect ophthalmoscopy, and
documented by retinal photographs. The retinitis must not be immediately
sight-threatening, i.e. retinal lesions must be greater than 1500 microns
from the edge of the optic disc, outside of the major temporal vascular
arcades, and greater than 3000 microns from the fovea.
People will be excluded who: have immediately sight-threatening retinitis;
only have retinal lesions which cannot be photographed; require continued
treatment with other medications such as antimetabolites, alkylating agents,
nucleoside analogs (except AZT as noted below under Administration); have
ocular media opacities (corneal, lenticular, or vitreal) which prevent
ophthalmologic and photographic retinal assessment; have ocular conditions
requiring immediate surgical correction, e.g. retinal tear, detachment; have
had previous treatment with anti-cytomegalovirus therapy, e.g. gan
cicyclovir, foscarnet, or CMV hyperimmune globulin; are receiving another
investigational drug other than aerosolized pentamidine; or who have
demonstrated hypersensitivity to acyclovir. Women who are pregnant, nursing
mothers, or who test positive on a pregnancy test, and men or women who are
not using adequate birth control measures are also excluded. Laboratory
tests must also be within certain limits (absolute neutrophil count greater
than or equal to 1000/mm^3; platelets count of greater than or equal to
50,000/mm^3; serum creatinine less than 1.5 mg/dl).
TERM: 16 weeks, with the option of continuing on "open-label" gancicyclovir
after the study period ends. Participants must use an effective method of
birth control during and after the conclusion of the study: 30 days for
women, 90 days for men.
ADMINISTRATION: Participants will be divided into two groups. The first
group will receive immediate gancicyclovir treatment. The second group will
receive delayed gancicyclovir treatment. While AZT is not permitted while
on the study (because both gancicyclovir and AZT cause bone marrow
suppression, and the combination can be too toxic), people in the delayed
treatment group can continue on AZT until their gancicyclovir treatment
starts. People in the delayed treatment group who show progression of their
retinitis will be eligible to start immediate gancicyclovir therapy.
Gancicyclovir is administered intravenously, usually through a Hickman or
similar catheter (which is a plastic tube in your chest which goes directly
into a vein), over the course of one hour. Gancicyclovir is given at 5
mg/kg once every twelve hours for the first two weeks, and then once a week
at 5 mg/kg for the next 14 weeks. If the participant develops severe side
effects, gancicyclovir therapy will be either at a reduced dosage,
suspended, or discontinued.
METHODOLOGY: Gancicyclovir (also known as dihydroxy-propoxymethyl guanine
or DHPG) interferes with the DNA synthesis necessary for cytomegalovirus to
reproduce.
NOTES: Participants must be referred by their physician. Side effects from
gancicyclovir range from lowered white blood cell counts, decreased platelet
counts, skin rashes, hives, nausea, vomiting, dizziness, bleeding and
bruising, irritation of the veins, and possible impairment of reproductive
or sexual function (possibly permanently). Other side effects which have
been observed include abnormalities in liver or kidney function, low blood
pressure, fainting, headache, anemia, swelling, fever, damage to nerves,
loss of hair, intestinal bleeding, seizures, loss of hearing, and p
sychological changes including confusion, irritability, nightmares,
hallucinations, or psychosis. Damage to eggs or sperm may result, which is
one of the reasons why contraception while on gancicyclovir is essential (in
addition to not passing HIV on to future offspring).
CONTROLS: None. All participants will receive gancicyclovir eventually,
but 50% of participants will receive it immediately, and 50% will receive it
on a delayed basis.
ORGANIZATION: George Washington University, one of the AIDS Treatment
Evaluation Units run by NIH
CONTACT: Interested people should have their doctor call Dr. David Parenti,
George Washington University, (202) 994-4716, or call Mary Beth Goldin at
(202) 994-2417 for more information.
***************************************************************************
TOXOPLASMOSIS PROTOCOLS
-------------------------------------------
PYRIMETHAMINE AND DAPSONE FOR TOXOPLASMOSIS
DESCRIPTION: Phase I/II study designed to evaluate the toxicity, tolerance
and effectiveness of combination therapy with dapsone and pyrimethamine for
the treatment of central nervous system toxoplasmosis in persons with AIDS
who are resistant to or intolerant of conventional therapy.
REQUIREMENTS: Participants must: have AIDS as defined by the Centers for
Disease Control; be at least 18 years of age; be able to sign an informed
consent; and be willing to sign a durable power of attorney. Participants
must have cerebral toxoplasmosis and either have been intolerant of or
failed conventional therapy (pyrimethamine and sulfadiazine).
TERM: Life-long if therapy is beneficial. Study will be stopped if the
participant deteriorates at 14 days of therapy or fails to improve at 21
days of therapy.
ADMINISTRATION: Participants will receive oral daily doses of pyrimethamine
25 mg, dapsone 100 mg, and leucovorin 10 mg. Adjustments of pyrimethamine
and dapsone will be made if the participant fails to respond. All
participants will be admitted to the NIH Clinical Center for induction of
therapy. After seven inpatient days, participants medically stable and
reliable will be discharged to continue therapy as outpatients.
Participants will be seen in the NIH outpatient clinic weekly for the first
three weeks, and every two weeks thereafter.
METHODOLOGY: Toxoplasmosis is a life-threatening parasitic infection caused
by a protozoa, toxoplasma gondii. Pyrimethamine, a dihydrofolate reductase
inhibitor and dapsone, a sulfone agent, are known to block folic acid
metabolism, an important pathway in both humans and toxoplasma organisms.
Leucovorin, mentioned above, allows the body's cells to bypass the blockade
without affecting the anti-protozoan activity. In combination, these drugs
have the potential to be at least as effective as the conventional regimen,
pyrimethamine and sulfadiazine, but less toxic, for treatment of
toxoplasmosis.
NOTES: Possible side effects include a decrease in white blood cell count
or platelet count, anemia, methemoglobinemia, hepatitis, kidney problems,
rash, nausea, and vomiting.
CONTROLS: None
ORGANIZATION: National Institutes of Health: National Institute of Allergy
and Infectious Diseases (NIAID)/National Cancer Institute (NCI)/Clinical
Center
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-9565
***************************************************************************
MISCELLANEOUS PROTOCOLS
----------------------------------------
BLOOD DRAWING STUDY
DESCRIPTION: Blood is drawn for research on the immune response to the AIDS
virus.
REQUIREMENTS: Patients must be positive for antibodies to HIV-1, without
severe anemia. Medication usage is acceptable.
TERM: Several hours as an out-patient at the NIH Clinical Center.
ADMINISTRATION: One unit of blood is drawn, the same amount that would be
given when donating blood for transfusion.
COMPENSATION: Participants in the study will receive compensation of
$30.00.
METHODOLOGY: The blood drawn will be used in research to fight HIV.
CONTROLS: Not applicable
ORGANIZATION: National Institutes of Health/National Heart, Lung, and Blood
Institute/Pulmonary Branch, Bethesda, MD 20892
CONTACT: Pulmonary Branch, (301) 496-2449
----------------------------------------
BRONCHOALVEOLAR LAVAGE STUDY
DESCRIPTION: Study to assess the impact of HIV-1 infection on lung defense
mechanisms.
REQUIREMENTS: Patients must be between the ages of 18 and 60, be positive
for antibodies to HIV, and not had active pulmonary opportunistic infections
(e.g. Pneumocystis Carinii Pneumonia or other lung disorders) in the last
three months. Infection prior to three months, current medication use or
Kaposi's sarcoma are not exclusions.
TERM: The study involves one full day as an in-patient at the NIH Clinical
Center.
ADMINISTRATION: Participants will receive a complete medical evaluation
including a medical history, physical examination, chest X-rays,
electrocardiogram, urinalysis, blood tests, lung function studies, and
bronchoscopy with washes for analysis of cells and potential pneumonias.
COMPENSATION: Participants in the study will receive compensation of
$122.00.
METHODOLOGY: Analysis will be made of the washes of the lungs so
researchers can gather more information on what organisms attack the lungs,
and how the lungs' defense mechanisms operate.
NOTES: No prescriptions are dispensed. Results of testing are made
available to the participant and a referring physician.
CONTROLS: Not applicable
ORGANIZATION: National Institutes of Health/National Heart, Lung, and Blood
Institute/Pulmonary Branch, Bethesda, MD 20892
CONTACT: Pulmonary Branch, (301) 496-2449
----------------------------------------
BRONCHOSCOPY STUDY
DESCRIPTION: A study to determine the existance of pneumocystis in
individuals with prior history of PCP and the presence of pneumocystis,
cytomegalovirus, or other pulmonary pathogens in asymptomatic HIV-positive
individuals without past history of PCP. A secondary goal is to determine
whether conventional and experimental laboratory techniques such as
bronchoscopy and sputum induction can detect the early presence of
cytomegalovirus, and how these findings correlate with future clinical
developments.
REQUIREMENTS: Participants must: be at least 18 years of age; be able to
sign an informed consent form; have a normal chest X-ray; and show no
respiratory symptoms such as cough, fever, chest pain, or shortness of
breath.
TERM: Approximately one to two days
ADMINISTRATION: Participants will not receive any therapeutic treatment.
Participants will be screened, and if eligible undergo the following:
1. Blood tests
2. Pulmonary function test, a breathing test which is done as an
outpatient and takes approximately 15-30 minutes
3. Two induced sputum collections, where the participant breathes in a
mist for appoximately 15 minutes, and then coughs into a sterile cup
4. Bronchoscopy with biopsy, a procedure that involves placing a thin
flexible tube into your airways, washing the cells of the lining of the lung
with a salt water solution, and obtaining several small pieces of lung
tissue under X-ray guidance. This tissue is then examined under a
microscope. The procedure is done under local anesthesia and involves
admission into the hospital for one to two days.
METHODOLOGY: Pneumocystis and cytomegalovirus (CMV) are the most common
life-threatening causes of morbidity and mortality in patients with HIV
infection. Whether these organisms are present in an asymptomatic HIV-
infected cohort with varied respiratory histories, and the role various
tests play in diagnosis of these infectious pulmonary pathogens is unclear.
Of special interest is determining the importance of various diagnostic
specimens in documenting the presence of CMV pneumonitis. To date, there is
no consensus about how best to diagnose CMV pulmonary infection. Due to t
he increase in PCP prophylactic therapy, it is likely that other pathogens
such as CMV will be a greater cause of morbidity and mortality.
CONTROLS: None
ORGANIZATION: National Institutes of Health: Clinical Center/National
Institute of Allergy and Infectious Diseases (NIAID)
CONTACT: Debbie Ogata-Arakaki, Building 10, Room 10D48, National Institutes
of Health, Bethesda, MD 20892, (301) 496-9565
----------------------------------------
GP-160 (VACCINE)
DESCRIPTION: Experimental vaccine against HIV
REQUIREMENTS: You must be male, negative (non-reactive) on the ELISA test
for antibodies to HIV, and have had no unsafe sex for at least three months
prior to the screening. Participants cannot be promiscuous or in an unsafe
sexual relationship with a HIV-positive partner. A commitment is required
to not have sex which will place you at risk for HIV infection (either oral
or anal, with or without condoms) for at least three months following
vaccination (a year is desired).
TERM: Approximately 13 months
ADMINISTRATION: Initial screening, blood work, and a tetanus/diptheria
booster shot for people who aren't current; followed by an intensive
physical examination four weeks later; then administration of the vaccine
by intramuscular injection. Required follow-up visits once a week for four
weeks, then once a month for the next year.
METHODOLOGY: gp-160 is the protein that forms the protein coat of HIV.
This vaccination is NOT a "dead" virus, so there is zero chance of HIV
infection from the vaccine. gp-160 is synthesized using recombinant DNA
techniques (gene splicing). The hope is that your body will respond to the
protein and form antibodies to it (just like any other vaccine). One result
of this is that if the vaccine works, volunteers may then test positive for
HIV antibodies on the ELISA test. The more sophisticated Western Blot test,
done by a competent laboratory, should be able to tell the differ ence
between HIV infection and antibodies formed in response to gp-160.
Volunteers will get notarized copies of their Western Blot tests before and
after participation in the study, as well as a detailed description. Be
warned, however, that insurance companies (both health and life) may still
discriminate against you because of testing positive for HIV antibodies, and
other problems could arise with regard to employment in the military, or the
State Department, etc.
NOTES: Because the study relies on the Western Blot test to make sure that
individuals do not have HIV before the study begins, 50% of the volunteers
have been rejected after the initial screening (because of problems in
getting a clear Western Blot test). The researchers think that this may be
because the Western Blot test is too sensitive, and is reacting to non-HIV
proteins. Until something can be proved, they are rejecting anyone who does
not have a completely clear Western Blot.
CONTROLS: Very few. One fifth of the volunteers at the highest dosage
levels will get a harmless substance called KLH as a control group to see
how their immune response differs from the immune response of the volunteers
getting gp-160. But, basically, almost all of the volunteers get the actual
vaccine.
ORGANIZATION: National Institutes of Health/National Institute of Allergy
and Infectious Diseases (NIAID)
CONTACT: Margaret Easter, Building 10, Room 11B-13, National Institutes of
Health, Bethesda, MD 20892 (Medical Center METRO stop). (301) 496-7196
----------------------------------------
HIV & HEART DISEASE STUDY
DESCRIPTION: Long-term study of heart disease in people who are infected
with HIV.
REQUIREMENTS: Participants must be HIV positive.
TERM: The study is expected to run until June, 1993.
ADMINISTRATION: Participants will go to the study center every four months,
and will undergo three non-invasive tests of their hearts: an EKG
(electrocardiogram), an echocardiogram, and a Signal Averaged EKG (a more
sensitive, computer-processed version of the EKG). Blood will also be drawn
for analysis. Study hours are on Tuesdays, from 8:00 a.m. to 1:00 p.m. If
abnormalities are detected, participants will be asked to return every two
months.
METHODOLOGY: The EKG and other tests help analyze the condition of your
heart. The blood work checks for antibodies to heart antigens. The two
primary heart diseases being watched for are cardiomyopathy (enlargement of
the heart), and pericardial effusions (which are fluids in the sack around
the heart).
Seventy percent of AIDS patients showed cardiac problems at autopsy, many of
these problems might have been amenable to treatment with appropriate drugs.
Monitoring can help detect these types of problems early enough that they
can be treated. Many people who aren't HIV-positive but have a history of
heart disease in their family undergo this type of monitoring as a matter of
routine.
No actual treatment is performed during this study. If problems are
detected, participants are referred to their physician for treatment. Full
cooperation and access to medical records will be provided by the
researchers.
NOTES: Participants will have their results evaluated by and be seen by a
cardiologist every time they come in for testing. Confidentiality of
patient records is maintained. Copies of all testing records are sent on
request to either the participant or the participant's physician.
CONTROLS: Not applicable
ORGANIZATION: George Washington University Hospital, Division of Cardiology
CONTACT: Sara Adams, Room 2440 North, George Washington University
Hospital, 901 23rd Street, N.W., Washington, DC 20037, (202) 994-3909
----------------------------------------
MEGACE
DESCRIPTION: This is a double-blind, controlled study of Megace (Megestrol
Acetate) in people with AIDS who have severe weight loss because of HIV.
REQUIREMENTS: Participants must have a diagnosis of AIDS according to the
CDC definition, with weight loss of at least 10% of normal body weight.
TERM: Three month study period, followed by a period in which the
participants can continue on their assigned drug, or go to "open-label"
megace where they are guaranteed to be receiving the actual drug.
Participants can go on "open-label" Megace if their weight loss continues
during study.
ADMINISTRATION: Participants will be divided into four groups: one group
will receive 800 mg/day of Megace, another group will receive 400 mg/day of
Megace; another group will receive 100 mg/day of Megace; and the fourth
group will receive a placebo. Megace is a suspension in a liquid which is
taken once per day, either before or after breakfast.
METHODOLOGY: Megace (Megestrol Acetate) is a derivative of progesterone
(one of two the female sex hormones) that has been used in the past to treat
breast cancer patients. The study is to determine the efficacy of Megace in
AIDS patients. Megace has been reported to stimulate appetite and weight
gain.
CONTROLS: Four arm, controlled study. This means that there is an 86%
chance that you will receive some level of Megace, and A 14% CHANCE THAT YOU
WILL RECEIVE A PLACEBO.
ORGANIZATION: Veterans Affairs Hospital Medical Center, in conjunction with
the Washington Hospital Center (participants do not have to be VA eligible);
also George Washington University AIDS Clinical Trials Unit.
CONTACT: Pat Kramer or John Scott, Veterans Affairs Medical Center, 50
Irving Street, N.W., Washington, DC 20422, (202) 745-8694; Mary Beth
Goldin, George Washington University AIDS Clinical Trials Unit, 2300 I
Street, N.W., Room 202, Washington, DC 20037, (202) 994-2417
***************************************************************************
OTHER PROTOCOLS
For the most up-to-date information, call the NIAID AIDS Trial Line at 1-
(800) TRIALS-A [874-2572].
Aerosolized pentamidine, long term, open-label, Georgetown University, Dr.
James Lavelle, (202) 687-8826
AZT & Acyclovir, double-blind, placebo-controlled, in mildly symptomatic
HIV+, Georgetown University, Dr. James Lavelle, (202) 687-8826
AZT & Chemotherapy for untreated HIV-related CNS lymphoma, George Washington
University, Dr. Rick Schulof, (202) 994-4200
B12/Folate for people on AZT, Georgetown University, Pamela Harding, (202)
687-7163
Neuro-psychiatric characterization of HIV+ people on AZT, Georgetown
University, Pim Brouwers, 687-4954
HIV+ with symptoms for study of physical and psychological needs, Catholic
University of America, Dr. Mary O'Brien, (301) 635-5400
Salivary Function in HIV+, National Institute of Allergy and Infectious
Diseases, Dr. Yeh, (301) 496-1478
Eye movement in asymptomatic gay men, National Institute of Allergy and
Infectious Diseases, Robert Lipman, (301) 496-6295
Eye examinations for people with AIDS and ARC, Whitman-Walker Clinic in
conjunction with Howard University, Dr. Basil Vareldzis, (202) 797-3534
Vaccine against HIV, Johns Hopkins University, Carol Hilton, (301) 955-7283
(collect)
***************************************************************************
Copyright (C) 1988,1989 by Washington HIV News, all rights reserved.
Permission is granted for non-commercial use only.
--
J. Philip Miller, Professor, Division of Biostatistics, Box 8067
Washington University Medical School, St. Louis MO 63110
phil@wubios.WUstl.edu - Internet (314) 362-3617 phil@wubios.wustl - bitnet
uunet!wucs1!wubios!phil - UUCP C90562JM@WUVMD - alternate bitnet