Aripiprazole Treatment for Methamphetamine Dependence Among High-risk Individuals
Condition: Substance Abuse; HIV Infections
MeSH terms: Substance-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      Studies demonstrate that methamphetamine (meth) use is associated with high-risk sexual
      behavior among men who have sex with men (MSM), putting meth-using MSM at extraordinarily
      high risk for transmitting or acquiring HIV. This study is a randomized, double-blind,
      placebo-controlled trial of the medication aripiprazole for methamphetamine-using
      individuals, including MSM, and will assess efficacy, acceptability, tolerability, safety,
      and adherence to study medication.
    

Detailed description: 
      Population-based surveys estimate that the prevalence of methamphetamine use is 20 times
      higher among men who have sex with men (MSM) compared to the general population.
      Methamphetamine-associated sexual risk behavior is also a driving force in the MSM HIV
      epidemic: methamphetamine use has been associated with increased number of sexual partners,
      unprotected sex acts, sexually transmitted infections (STIs), and HIV acquisition. Despite
      these alarming data, relatively few interventions have been tested among
      methamphetamine-using MSM. Among heterosexual non-injection drug users, methamphetamine use
      has been associated with well characterized risks for HIV and STDs including increased
      numbers of sexual partners, less condom use than non-methamphetamine users, engaging in sex
      work, and self-reported history of STDs. In parallel with the continued testing of behavioral
      approaches, we believe the time has come to test the feasibility and acceptability of
      pharmacologic interventions to reduce methamphetamine use among high-risk individuals.
      Pharmacologic approaches to treating substance use have been successful in treating nicotine,
      alcohol, and heroin dependencies. Preliminary dosing studies demonstrate that aripiprazole
      (Abilify), an FDA-approved, well-tolerated antipsychotic and partial dopamine agonist,
      reduced the effects of methamphetamine in humans and exhibited a good safety profile. We
      propose to expand upon these promising results by conducting a randomized, double-blind,
      placebo-controlled pilot study of aripiprazole among sexually-active,
      methamphetamine-dependent individuals.

      The specific aims of this study are:

        1. To test the hypothesis that aripiprazole 20 mg daily will reduce methamphetamine use
           significantly more than placebo among methamphetamine-dependent individuals, as
           determined by the proportion of methamphetamine-negative urines and by self-report of
           methamphetamine use in the aripiprazole versus placebo group.

        2. To measure the acceptability of aripiprazole and placebo among methamphetamine-dependent
           individuals, by determining (via electronic pill caps and self-report) medication
           adherence to aripiprazole and placebo.

        3. To measure the safety and tolerability of aripiprazole and placebo among
           methamphetamine-dependent individuals, as determined by the number of adverse clinical
           events in the aripiprazole and placebo arms.

      If promising, study results will be used to design larger, definitive clinical trials to
      determine the efficacy of aripiprazole in reducing methamphetamine use and corresponding
      methamphetamine-associated sexual risk among MSM. This pilot study is therefore designed to
      reflect the structure of such trials. We will enroll 90 sexually active,
      methamphetamine-dependent individuals who will be randomized 1:1 to receive aripiprazole
      (n=45) or placebo (n=45) for 12 weeks. Because we are testing a drug for a new indication in
      a new population, we will include extensive safety parameters, as done in prior studies of
      pharmacologic interventions among substance users. We will also include both urine testing
      and extensive behavioral risk assessments because we anticipate that future definitive
      efficacy trials will analyze both substance use and sexual risk behavior outcomes. Study
      participants will be seen at the San Francisco Department of Public Health AIDS Office where
      they will provide urines for drug testing and participate in substance use counseling. All
      participants will receive HIV risk-reduction counseling. Behavior will be assessed using
      standardized measures via audio computer-assisted self-interview (ACASI).
    

Intervention name(s): Aripiprazole; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Sugar pill manufactured to mimic Aripiprazole gel caps.
Other intervention name(s): Abilify
Intervention MeSH terms: Aripiprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Methamphetamine; HIV; MSM; HIV Seronegativity