Aripiprazole to reduce methamphetamine use among MSM with high-risk HIV behaviors

描述（由申请人提供）：基于人群的调查估计，与一般人群相比，男男性行为者（MSM）使用甲基苯丙胺（冰毒）的流行率高出20倍。与冰毒有关的性危险行为也是男男性接触者艾滋病毒流行的一个推动因素：冰毒的使用始终与高风险的性行为和性传播疾病，包括艾滋病毒有关。尽管有这些令人震惊的数据，但在使用冰毒的男男性行为者中测试的干预措施相对较少，而且没有研究测试药物干预在减少这一人群中使用冰毒的有效性。初步研究表明，阿立哌唑（Abilify）是一种经fda批准的耐受性良好的抗精神病药和部分多巴胺激动剂，可以减少冰毒对人体的影响，减少对冰毒的渴望，并显示出良好的安全性。部分激动剂——具有靶受体亲和力但内在活性低的配体——已被证明对治疗阿片和尼古丁依赖有效。针对支持阿立哌唑和部分激动剂方法的令人信服的证据，我们建议进行一项随机、双盲、安慰剂对照的中等规模（60名参与者）和长度（90天随访）的试验，以评估阿立哌唑在减少冰毒依赖、性活跃的男男性行为者使用冰毒方面的疗效。我们的具体目标是：1)通过阿立哌唑组与安慰剂组的甲基苯丙胺尿阴性比例和自我报告甲基苯丙胺使用情况，验证阿立哌唑每日20毫克比安慰剂更能显著减少甲基苯丙胺依赖的男男性行为者使用甲基苯丙胺的假设。2)通过测定（通过电子药帽和自我报告）阿立哌唑和安慰剂的服药依从性，衡量冰毒依赖男男性行为者对阿立哌唑和安慰剂的可接受性。3)衡量阿立哌唑和安慰剂在冰毒依赖男男性行为者中的安全性和耐受性，通过阿立哌唑组和安慰剂组的不良临床事件数量来确定。所有参与者都将接受降低艾滋病毒风险的咨询和简短的药物使用咨询。如果有希望，我们预计研究结果将用于设计一项III期研究，以确定阿立哌唑对减少冰毒使用的影响是否会显著降低冰毒相关的性风险，如果试验样本量合适，还会降低艾滋病毒发病率。

DESCRIPTION (provided by applicant): Population-based surveys estimate that the prevalence of methamphetamine (meth) use is 20 times higher among men who have sex with men (MSM) compared to the general population. Meth-associated sexual risk behavior is also a driving force in the MSM HIV epidemic: meth use is consistently associated with high-risk sexual behavior and sexually transmitted diseases, including HIV. Despite these alarming data, relatively few interventions have been tested among meth-using MSM, and no studies have tested the efficacy of pharmacologic interventions in reducing meth use in this population. Pilot studies demonstrate that aripiprazole (Abilify), an FDA-approved, well-tolerated antipsychotic and partial dopamine agonist, reduces the effects of meth in humans, decreases meth craving, and exhibits an excellent safety profile. Partial agonists - - ligands with target receptor affinity but low intrinsic activity - - have already been shown to be effective in treating opiate and nicotine dependence. In response to the compelling evidence supporting aripiprazole and the partial agonist approach, we propose conducting a randomized, double-blind, placebo- controlled trial of intermediate size (60 participants) and length (90 days of follow-up) to assess the efficacy of aripiprazole in reducing meth use among meth-dependent, sexually active MSM. Our specific aims are: 1) To test the hypothesis that aripiprazole 20 mg daily will reduce meth use significantly more than placebo among meth-dependent MSM, as determined by the proportion of meth-negative urines and by self- report of meth use in the aripiprazole versus placebo group. 2) To measure the acceptability of aripiprazole and placebo among meth-dependent MSM, 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 meth-dependent MSM, as determined by the number of adverse clinical events in the aripiprazole and placebo arms. All participants will receive HIV risk-reduction counseling and brief substance use counseling. If promising, we anticipate that study results will be used to design a phase III study to determine if aripiprazole's effects on reducing meth use lead to significant reductions in meth-associated sexual risk and, if the trial sample size is appropriate, HIV incidence.