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（meth）的使用在 MSM 中非常常见，尤其是感染 HIV 的 MSM。 HIV 阴性和 HIV 阳性 MSM 的冰毒使用率分别是美国普通成年人口的 13 倍和 34 倍。冰毒的使用与 MSM 中 HIV 相关的性危险行为独立相关，并且可能成为 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 HIV 危险行为以及优化 ART 和 PrEP 依从性，作为重要的 HIV 预防和护理干预措施。 MSM 占美国新感染病例的三分之二。尽管国内艾滋病毒流行持续，而且男男性行为者中冰毒使用率很高，但很少有干预措施被证明对这一人群有效。 目前还没有 FDA 批准的甲基苯丙胺药物治疗方法，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曲酮和生态瞬时干预（ION+EMI）增强的间歇性口服纳曲酮对冰毒使用治疗的疗效来解决这一差距。纳曲酮是一种 µ-阿片受体拮抗剂，对于吸食冰毒的 MSM 来说是一种很有前景的药物。冰毒在血液中迅速代谢为安非他明，纳曲酮已显示出减少安非他明复发的功效。此外，新出现的证据表明，针对当前环境的生态瞬时干预（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关于间歇性纳曲酮的初步研究发现，与安慰剂相比，每周至少使用 1 天的甲基吸毒男男性行为者在按需使用纳曲酮治疗时，其吸毒天数和性风险行为显着减少。在试点项目中，参与者报告称，他们在渴望冰毒或预期使用冰毒的日子里，有 64% 都在服用研究药物。为了以这项研究的结果为基础，我们建议在一项疗效试验中评估间歇性纳曲酮治疗冰毒的使用，该试验通过 EMI 增强，该试验响应参与者的渴望或预期的冰毒使用水平，在参与者最能从纳曲酮中受益的时期提供即时用药提醒。 该提案题为“ION+EMI 研究：使用甲基苯丙胺的 MSM 间歇性口服纳曲酮通过生态瞬时干预增强”是一项双盲、安慰剂对照 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) 接受为期 12 周的按需间歇性口服纳曲酮 50 mg，增强剂为甲基苯丙胺。 EMA 通知的 EMI 平台，或具有 EMI 的按需安慰剂。主要结果将在试验完成后进行评估，通过甲基阳性尿液样本的比例来衡量 （目标 1）；通过 ACASI 进行月度调查，获取性风险行为数据，考虑 PrEP 和病毒载量状态（目标 2）；通过药物水平或病毒载量测试来确定 PrEP 或 ART 的依从性（目标 3）。