Mirtazapine to Reduce Methamphetamine Use Among MSM With High-risk HIV Behaviors
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 MSM, putting meth-using MSM at extraordinarily high risk for transmitting or
      acquiring HIV. This study of intermediate size (60 participants) and length (3 months of
      follow-up) will assess the efficacy of mirtazapine in reducing methamphetamine use among
      high-risk MSM.
    

Detailed description: 
      Methamphetamine use is especially prevalent among men who have sex with men (MSM).
      Population-based surveys report methamphetamine use rates 20 times higher among MSM compared
      with the general population. Methamphetamine use is also a driving force in the MSM HIV
      epidemic: methamphetamine use has been associated with increased number of sexual partners,
      unprotected sex acts, and sexually transmitted infection (STI) and HIV acquisition. Despite
      these alarming data, relatively few interventions have been tested among
      methamphetamine-using MSM, and no studies have tested the efficacy of pharmacologic
      interventions in reducing methamphetamine use in this population. In parallel with the
      continued testing of behavioral approaches, we believe the time has come to test
      pharmacologic interventions to reduce methamphetamine use among MSM. Pharmacologic approaches
      to treating substance use have been successful in treating nicotine, alcohol, and heroin
      dependence. No studies have tested a pharmacologic intervention to reduce methamphetamine use
      among MSM at high risk for HIV acquisition and transmission. A recent pilot study found that
      mirtazapine, a drug with dual dopaminergic and serotonergic properties, significantly reduced
      methamphetamine withdrawal symptoms when compared to placebo over a two-week period among
      Thai men in a drug probation center. Mirtazapine is a commonly used, FDA-approved
      antidepressant; however, in the Thai study its effects on methamphetamine withdrawal were
      independent of its effects on depressive symptoms, suggesting a direct effect of mirtazapine
      on treating methamphetamine dependence. We propose to expand upon these promising pilot
      results by conducting a study of intermediate size (60 participants) and length (3 months of
      follow-up) to assess the efficacy of mirtazapine in reducing methamphetamine use among
      high-risk MSM.

      The specific aims of our study are:

        1. To test the hypothesis that mirtazapine 30 mg daily will reduce methamphetamine use
           significantly more than placebo among methamphetamine-dependent MSM, as determined by
           the proportion of methamphetamine-negative urines and by self-report of methamphetamine
           use in the mirtazapine versus placebo group.

        2. To measure the acceptability of mirtazapine and placebo among methamphetamine-dependent
           MSM, by determining (via electronic pill caps and self-report) medication adherence to
           mirtazapine and placebo.

        3. To measure the safety and tolerability of mirtazapine and placebo among
           methamphetamine-dependent MSM, as determined by the number of adverse clinical events in
           the mirtazapine and placebo arms.

      If promising, study results will be used to design a phase III clinical trial to determine if
      mirtazapine's effects on reducing methamphetamine use lead to reductions in
      methamphetamine-associated sexual risk. We have chosen first to conduct a 3-year
      intermediate-sized trial in order to determine if mirtazapine reduces methamphetamine use and
      whether mirtazapine demonstrates good acceptability and tolerability among a population with
      methamphetamine-associated high-risk sexual behaviors. If this proves to be the case, we
      believe our study results will provide strong support for a much larger trial to test the
      hypothesis that mirtazapine-driven reductions in methamphetamine use will result in
      corresponding decreases in sexual risk behavior. This study is therefore designed to reflect
      the structure of a larger HIV-risk reduction trial and includes both substance use and sexual
      risk behavior measures. We will enroll sexually active, methamphetamine-dependent MSM (either
      HIV-negative or HIV-positive) who will be randomized 1:1 to receive mirtazapine or placebo
      for 90 days. Because no medications have been approved to treat methamphetamine dependence,
      we include extensive safety parameters, as is required by the Food and Drug Administration
      (FDA) when testing a medication for a new indication in a new population. Participants will
      be seen weekly for urine drug testing and for brief substance use counseling. All will
      receive HIV risk-reduction counseling. Behavior will be assessed using standardized measures
      via audio computer-assisted self-interview (ACASI).
    

Intervention name(s): mirtazapine; placebo
Intervention type(s): Drug; Drug
Intervention description(s): mirtazapine 30 mg daily for 3 months; placebo 30 mg daily for 3 months
Other intervention name(s): Remeron
Intervention MeSH terms: Mirtazapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Methamphetamine; HIV; MSM; HIV Seronegativity