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

ION EMI 研究：间歇性口服纳曲酮通过生态瞬时干预增强使用甲基苯丙胺的 MSM

• 批准号: 10253657
• 负责人: Glenn-Milo Santos
• 金额: $ 32.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10253657
• 关键词: AIDS prevention; Accounting; Address; Adherence; Adult; Amphetamines; Anal Sex; Attenuated; Behavioral; Blood Circulation; Caring; Computers; Counseling; DSM-V; Data; Detection; Disease; Dose; Double-Blind Method; Ecological momentary assessment; Enrollment; Epidemic; Exposure to; FDA approved; HIV; HIV Seronegativity; HIV Seropositivity; HIV risk; Health behavior; High Prevalence; Individual; Infection; Interruption; Intervention; Intervention Studies; Laboratories; Lead; Measures; Methamphetamine; Naltrexone; Opioid Antagonist; Oral; Participant; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase; Pilot Projects; Placebos; Population; Randomized; Regimen; Relapse; Reporting; Research; Risk Behaviors; Safety; Sampling; Schedule; Surveys; Testing; Time; Toxic effect; United States; Urine; Viral Load result; Visit; amphetamine use; antiretroviral therapy; base; cis-male; craving; double-blind placebo controlled trial; effective intervention; efficacy evaluation; efficacy trial; eligible participant; medication compliance; men who have sex with men; methamphetamine use; mu opioid receptors; neglect; pre-exposure prophylaxis; prevent; primary outcome; randomized trial; response; sexual risk behavior; sexually active; substance use; therapy adherence

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).

甲基苯丙胺（冰毒）的使用在男男性行为者中非常普遍，特别是感染艾滋病毒的男男性行为者。艾滋病毒阴性和艾滋病毒阳性的男男性行为者中使用甲氧西林的流行率分别是美国普通成年人的13倍和34倍。甲基苯丙胺的使用与男男性接触者中艾滋病毒相关的性风险行为独立相关，并且可以作为ART和暴露前预防（PrEP）依从性的障碍。因此，减少冰毒使用的有效干预措施也可以通过减少与物质相关的艾滋病毒风险行为，优化ART和PrEP依从性，作为重要的艾滋病毒预防和护理干预措施。MSM占美国新感染病例的三分之二。尽管这种持续的国内艾滋病毒流行病和高流行率的甲基使用的男男性行为者，很少有干预措施已被证明是有效的，在这一人群。 没有FDA批准的用于甲基苯丙胺使用的药物疗法，这是治疗领域的一个主要空白。我们试图通过评估间歇性口服纳洛酮与生态瞬时干预（ION+EMI）用于冰毒使用治疗的疗效来解决这一差距。纳洛酮是一种μ-阿片受体拮抗剂，是一种很有前途的药物。甲基苯丙胺在血液中迅速代谢为苯丙胺，纳洛酮在减少苯丙胺使用复发方面显示出疗效。此外，新出现的证据表明，对当下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，例如增加药物剂量。我们小组进行的一项间歇性纳洛酮的试点研究发现，与安慰剂相比，每周至少使用1天的使用冰毒的MSM在使用冰毒的天数和性风险行为方面有更大的减少。在试验中，参与者报告说，在他们渴望冰毒或预期使用冰毒的日子里，有64%的人服用了研究药物。为了建立在这项研究的结果，我们建议评估间歇性纳洛酮治疗冰毒使用的疗效试验增强了EMI，响应参与者的渴望或预期的冰毒使用水平，以提供在参与者最受益于纳洛酮期间的即时药物提醒。 这项名为“ION+EMI研究：间歇性口服纳洛酮，对使用甲基苯丙胺的MSM进行生态瞬时干预”的提案是一项双盲，安慰剂对照的2b期试验，其中54名使用甲基苯丙胺的MSM将被随机分配（2：1）接受12周的间歇性口服纳洛酮50 mg，通过EMA知情的EMI平台增强，或根据需要服用安慰剂。主要结局将在试验完成时评估，通过甲基苯丙胺阳性尿样的比例进行测量 (Aim 1）、性风险行为数据，占PrEP和病毒载量状态，通过ACASI每月调查（目标2）;和PrEP或ART坚持药物水平或病毒载量测试（目标3）。