Intermittent Naltrexone among Polysubstance Users

描述（由申请人提供）：甲基苯丙胺（冰毒）的使用和酗酒（男性定义为一次喝五杯或更多）与显著的发病率和死亡率相关。在美国，使用冰毒和酗酒的经济成本分别超过230亿美元和1700亿美元。在男男性接触者中，使用冰毒和酗酒的比例分别是普通美国成年人的20倍和3.5倍。此外，这两种物质一直与MSM（占美国新感染病例的一半以上）中的无保护性行为和艾滋病毒血清转化有关。因此，通过减少与药物相关的艾滋病毒风险行为，减少冰毒使用和酗酒的有效干预措施也可能作为一种重要的艾滋病毒预防策略。纳曲酮是一种u-阿片受体拮抗剂，对于使用冰毒和酗酒的男男性行为者来说是一种很有前途的药物。纳曲酮已显示出减少安非他命复发的功效，并且已被fda批准用于治疗酒精依赖。口服纳曲酮价格低廉，毒性很小，但纳曲酮的标准日常治疗方案存在问题，因为患者会忘记服药。鉴于每日给药的挑战，已经提出了替代方案计划，以提高疗效并扩大可能受益的人群。一种方法是间歇性地有针对性地使用纳曲酮，即个人在预期药物使用或在渴望期间根据需要服用药物。在暴露于安非他明之前服用纳曲酮可显著减轻渴望，并且有针对性的纳曲酮已显示出减少大量饮酒的功效。然而，目前还没有研究评估纳曲酮在使用冰毒和酗酒的男男性行为者中的间歇性靶向剂量。多物质使用模式在男男性行为者中很常见，迫切需要对服用一种以上物质的人进行研究。本研究的目的是确定目标剂量的纳曲酮是否可行，耐受性和可接受的非依赖性吸毒和酗酒的男男性行为者。设计：这是一项针对口服纳曲酮的先导、双盲、安慰剂对照试验。30名非依赖性、间歇性使用冰毒和酗酒的男男性行为者将被随机分配接受8周的50毫克纳曲酮或安慰剂治疗，根据需要服用纳曲酮以减轻对冰毒的渴望或减少酗酒。参与者将每两周接受一次学习药物和药物使用咨询。安全评估和行为调查将在两周一次和每月一次的访问中完成。可行性、耐受性和可接受性（具体目标1-3）将通过入组率和保留率、不良事件频率、参与者对靶向剂量和药物依从性的评估来评估。冰毒使用和饮酒的结果将通过每日短信和每两周一次的时间跟踪来评估（探索性目标）。性行为将通过月度调查进行评估（探索性目标）。GEE逻辑模型将用于比较MSM在冰毒渴求和酗酒期间服用药物的比例。GEE二项和负二项模型将用于评估对冰毒使用、饮酒和性行为的治疗效果。

DESCRIPTION (provided by applicant): Methamphetamine (meth) use and binge drinking (defined for men as drinking five or more drinks on one occasion) are associated with significant morbidity and mortality. The economic cost of meth use and binge drinking in the US exceeds $23 and $170 billion, respectively. Among MSM, meth use and binge drinking are up to 20 and 3.5 times more prevalent than in the general U.S. adult population, respectively. Moreover, these two substances are consistently associated with unprotected sex and HIV seroconversion among MSM, who comprise over half of the new infections in the U.S. Thus, effective interventions to reduce meth use and binge drinking may also function as an important HIV prevention strategy by reducing substance-related HIV risk behavior. Naltrexone, a u-opioid receptor antagonist, is a promising agent for meth-using and binge-drinking MSM. Naltrexone has shown efficacy in reducing relapse to amphetamines and is FDA-approved for alcohol dependence. Oral naltrexone is inexpensive and has few toxicities but the standard daily regimen for naltrexone is problematic as patients forget to take the medication. Given the challenges in daily dosing, alternate regimen schedules have been proposed to increase efficacy and expand the population that may benefit. One approach is intermittent targeted administration of naltrexone, whereby individuals take the medication as needed in anticipation of substance use or during periods of craving. Administration of naltrexone prior to exposure to amphetamines significantly attenuates craving and targeted naltrexone has shown efficacy in reducing heavy alcohol use. However, there have been no studies assessing intermittent targeted dosing of naltrexone among meth-using and binge-drinking MSM. Polysubstance use patterns are common among MSM-studies among those who take more than one substance are urgently needed. The aims of this study are to determine whether targeted dosing of naltrexone is feasible, tolerable and acceptable among non-dependent meth-using and binge-drinking MSM. Design: This is a pilot, double-blind, placebo-controlled trial of targeted oral naltrexone. Thirty non-dependent, episodic meth-using and binge-drinking MSM will be randomly assigned to receive 8 weeks of naltrexone 50 mg or placebo, to be taken on an as-needed basis to attenuate meth craving or reduce binge drinking. Participants will be seen bi-weekly to receive study drug and substance use counseling. Safety assessments and behavioral surveys will be completed at bi-weekly and monthly visits. Feasibility, tolerability, and acceptability (Specific Aims 1-3) will be assessed with enrollment and retention rates, frequency of adverse events, participant evaluation of targeted dosing and medication adherence. Meth use and drinking outcomes will be assessed via daily text messages and bi-weekly timeline follow-back (Exploratory Aims). Sexual behaviors will be assessed via monthly surveys (Exploratory Aims). GEE logistic models will be used compare the proportions of MSM taking medication during periods of meth craving and binge drinking. GEE binomial and negative binomial models will be used to assess treatment effects on meth use, drinking and sexual behavior. PUBLIC HEALTH RELEVANCE: Meth use and binge drinking are linked to HIV-related sexual risk behaviors and HIV infection among men who have sex with men (MSM). This study will examine the feasibility, tolerability and acceptability of taking naltrexone on an as-needed basis during periods of meth craving and in anticipation of drinking among MSM. This study will contribute to the field of substance use and HIV prevention research for a marginalized and disproportionately impacted population.