Abrams Protocol Submitted Anew
Donald Abrams, M.D.
UC-San Francisco
Below is a summary of the protocol, "Short-term Effects of
Cannabinoids in HIV Patients" which was submitted by Dr. Donald
Abrams, et al., UC-San Francisco, to the National Institutes of Health
(NIH) by a May 1, 1997 grant deadline. If accepted by the NIH, this study
would cost nearly a million dollars and would take three years to
complete. MAPS donated $5,000 for the preparation of this grant
application. NIH's decision regarding this application will be announced
before the end of September, 1997.
Summary
Our primary aim is to determine the safety/toxicity profile of
cannabinoids in persons with HIV infection. We propose to do this by
conducting a randomized, prospective study whose primary goal is to
determine the short-term effects of smoked marijuana on the
pharmacokinetics of indinavir, the immune system and the level of HIV-1
viral load in persons with HIV-1 infection. The study will be composed of
three successive phases. The first phase will be a 4-day lead-in period in
which baseline measurements a re obtained. This will be followed
immediately by a 21-day intervention phase in which subjects receive
either marijuana cigarettes (Group A), dronabinol capsules (Group B), or
placebo capsules (Group C). Subjects in Group A will smoke one 4%
THC-content marijuana cigarette three times daily, one hour prior to each
meal. Group B and C subjects will receive dronabinol 2.5 mg or placebo
three times daily, one hour prior to meals. In the last phase, subjects
will be evaluated as out-patients (with no intervention) on days 28, 35
and 32. Subjects will be hospitalized in the General Clinical Research
Center (GCRC) at San Francisco General Hospital for the first two phases
of the trial (25 days) because, at present, legal use of smoked marijuana
is restricted to medically supervised settings. The inpatient setting
also permits us to measure plasma THC levels as a means to assess the
total dose delivered, and to rigorously assess the safety parameters and
measures of possible efficacy, including appetite, food intake, body
composition and weight. Eligible subjects will be currently receiving
indinavir and will be experienced marijuana users. The primary outcomes
are change from baseline in (1) HIV-1 viral load and (2) indinavir
concentration (area under the curve). Because both indinavir and
dronabinol are metabolized in the liver, interactions between these
treatments could alter the concentration of indinavir, thus increasing its
toxicity or decreasing its efficacy. In turn, lower indinavir
concentration could result in an increase in viral load. We include
Control Group B (dronabinol capsules) in order to simultaneously evaluate
these outcomes in subjects treated according to the current standard of
care. We include Control Group C (placebo capsules) to estab lish baseline
values under out experimental conditions. We will also summarize the
short-term effects of smoked marijuana on variables associated with HIV-1
wasting syndrome by measuring changes over 21 days of use in endocrine
function, appetite, energy intake, body composition and weight. If the
current study demonstrates that smoked marijuana does not have the serious
short-term side effects studied here, we would next research safety and
efficacy of the chronic use of marijuana for HIV-associated anor exia and
weight loss. These data will help to identify the most powerful measures
to assess efficacy and provide estimates of effect size and variance.
Questions may be directed to:
Donald Abrams, M.D.
Community Consortium
3180 18th St., Suite 210
San Francisco, CA 94110
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