The ION+EMI Study: Intermittent Oral Naltrexone enhanced with an Ecological Momentary Intervention for Methamphetamine-using MSM

甲基苯丙胺在男男性接触者中非常普遍，特别是感染艾滋病毒的男男性接触者。在HIV阴性和HIV阳性的男男性接触者中，冰毒使用率分别是普通美国成年人的13倍和34倍。冰毒的使用与MSM中与艾滋病毒相关的性危险行为独立相关，并可能成为坚持抗逆转录病毒治疗和接触前预防(PrEP)的障碍。因此，减少冰毒使用的有效干预措施也可以作为一种重要的艾滋病毒预防和护理干预措施，减少与物质相关的艾滋病毒危险行为，并优化ART和PrEP的遵守情况。男男性接触者占美国新增感染人数的三分之二。尽管国内艾滋病毒持续流行，男男性同性恋者中冰毒使用率很高，但很少有干预措施被证明在这一人群中有效。 目前还没有FDA批准的甲基苯丙胺药物疗法，这是治疗领域的一个主要缺口。我们试图通过评估间歇性口服纳曲酮和生态瞬时干预(离子+EMI)对冰毒治疗的有效性来解决这一差距。纳曲酮是一种µ-阿片受体拮抗剂，是治疗使用冰毒的MSM的有前途的药物。冰毒在血液中迅速代谢为安非他明，纳曲酮在减少安非他明复吸方面显示出有效性。此外，新出现的证据表明，对即刻环境做出反应的生态瞬时干预(EMI)可以导致积极的健康行为，如增加用药剂量。我们小组对间歇性纳曲酮进行的一项初步研究发现，与安慰剂相比，每周至少使用一天的使用冰毒的MSM在按需使用纳曲酮治疗时，使用冰毒的天数和性危险行为的减少幅度明显更大。在试点中，参与者报告说，他们渴望冰毒或预期冰毒使用的天数中有%服用研究药物。为了在这项研究的结果基础上，我们建议在一项疗效试验中评估间歇性纳曲酮治疗冰毒使用的情况，该试验通过一种对参与者渴望或预期的冰毒使用水平做出反应的EMI来增强，以在参与者将从纳曲酮中受益最大的时期提供即时用药提醒。 这项名为“离子+EMI研究：使用甲基苯丙胺的间歇口服纳曲酮强化生态瞬间干预”的2b期试验是一项双盲、安慰剂对照的2b期试验，54名使用甲基苯丙胺的MSM将被随机分配(2：1)接受12周的间歇口服纳曲酮50毫克，并加入EMA通知的EMI平台，或根据需要接受安慰剂与EMI的联合治疗。初步结果将在试验完成后根据冰毒阳性尿样的比例进行评估 (目标1)；通过ACASI进行的月度调查提供的性危险行为数据，说明PrEP和病毒载量状况(目标2)；通过药物水平或病毒载量测试获得PrEP或ART依从性(目标3)。

Methamphetamine (meth) use is very common among MSM, particularly MSM living with HIV. Meth use among HIV-negative and HIV-positive MSM is up to 13 and 34 times more prevalent than in the general U.S. adult population, respectively. Meth use is independently associated with HIV-related sexual risk behaviors among MSM and can function as a barrier to ART and pre-exposure prophylaxis (PrEP) adherence. Thus, effective interventions to reduce meth use may also function as an important HIV prevention and care intervention by reducing substance-related HIV risk behavior, and optimizing ART and PrEP adherence. MSM comprise two-thirds of the new infections in the United States. Despite this continued domestic HIV epidemic and the high prevalence of meth use among MSM, few interventions have proven effective in this population. There are no FDA-approved pharmacotherapies for methamphetamine use, a major gap in the treatment field. We seek to address this gap by evaluating the efficacy of intermittent oral naltrexone enhanced with an ecological momentary intervention (ION+EMI) for meth use treatment. Naltrexone, a µ-opioid receptor antagonist, is a promising agent for meth-using MSM. Meth is rapidly metabolized to amphetamine in the bloodstream and naltrexone has shown efficacy in reducing relapse to amphetamine use. Additionally, emerging evidence suggests that ecological momentary interventions (EMI) that respond to in-the-moment contexts can lead to positive health behaviors, such as increasing medication dosing. A pilot study of intermittent naltrexone conducted by our group found that meth-using MSM who used at least 1 day per week had significantly greater reductions in meth-using days and sexual risk behaviors when treated with as-needed naltrexone, compared to placebo. In the pilot, participants reported taking study drug 64% of the days that they craved meth or anticipated meth use. To build on the results of this study, we propose to evaluate intermittent naltrexone to treat meth use in an efficacy trial enhanced by an EMI that responds to participant’s levels craving or anticipated meth use to provide in-the-moment medication reminders during periods when participants would most benefit from naltrexone. This proposal, entitled “The ION+EMI Study: Intermittent Oral Naltrexone enhanced with an Ecological Momentary Intervention for Methamphetamine-using MSM” is a double-blind, placebo-controlled phase 2b trial in which 54 meth-using MSM will be randomly assigned (2:1) to receive 12 weeks of as-needed intermittent oral naltrexone 50 mg enhanced with an EMA-informed EMI platform, or as-needed placebo with EMI. Primary outcomes will be assessed upon trial completion as measured by proportion of meth-positive urine samples (Aim 1); sexual risk behavior data, accounting for PrEP and viral load status, through monthly surveys via ACASI (Aim 2); and PrEP or ART adherence by drug levels or viral load test (Aim 3).