The Better THAN Study: Targeting Heavy Alcohol with Naltrexone among MSM

描述(由申请人提供)：针对RFA-RM-13-009，我们建议评估靶向剂量口服纳曲酮在有感染或传播艾滋病毒风险的非依赖型酗酒MSM中的疗效。狂饮(定义为男性一次喝五杯或五杯以上)，也被称为间歇性重度饮酒，在美国非常普遍。2010年，(过去30天)酗酒的总体估计流行率为17%。在每年因过度饮酒而死亡的8万人中，酗酒占了一半以上。2006年，在美国，酗酒造成的经济损失超过1700亿美元。国家艾滋病毒行为监测数据表明，57%的男男性行为者(MSM)报告酗酒(过去30天)。MSM中的酗酒与无保护措施的性行为和艾滋病毒感染独立相关。到目前为止，酗酒是男男性接触者中感染艾滋病毒最普遍的原因，2006年美国56,300名新感染艾滋病毒的人中，男男性接触者占一半以上。因此，减少男男性接触者酗酒的有效干预措施可能通过减少与酒精相关的性行为而起到预防艾滋病的重要作用。尽管在MSM中酗酒的高流行率和国内艾滋病毒的持续流行，但很少有酒精干预被证明在这一人群中有效。口服纳曲酮是FDA批准的治疗酒精依赖的低成本药物，毒性很小。纳曲酮是一种�类固醇受体拮抗剂，可减弱酒精的奖赏效应。纳曲酮的标准每日口服方案阻碍了依从性，已经提出了替代方案以增加药物的有效性，并扩大可能从这种药物干预中受益的人群。一种有希望的方法是间歇性的、有针对性的纳曲酮给药，即个人在预计会大量饮酒的情况下，根据需要服用药物。初步研究已经观察到，靶向纳曲酮在减少重度酒精使用方面有效，特别是对男性。然而，还没有关于在酗酒的MSM中评估靶向纳曲酮的疗效研究，也没有旨在减少相关艾滋病毒危险行为的试验。本研究的目的是评价靶向纳曲酮治疗酗酒MSM的疗效。研究设计：这是一项双盲、安慰剂对照试验，包括120名酗酒的MSM和12周的纳曲酮50 mg，预计将大量饮酒。不同族裔和种族的参与者将通过受访者驱动的抽样进行招募。MSM每周都会接受酒精代谢物尿液测试，研究配药和酒精使用的简短咨询。安全评估和行为调查将按月完成。对饮酒和与酒精相关的性行为(目标1-3)的有效性将通过每周时间线回访、乙基葡萄糖醛酸(EtG)阳性尿液筛查和计算机管理的每月干预措施进行评估。耐受性和可接受性(目标4)将通过跟踪不良事件和用药依从性进行评估。GEE模型将被用来估计重复研究结果的治疗效果。

DESCRIPTION (provided by applicant): In response to RFA-RM-13-009, we propose to evaluate the efficacy of targeted dosing of oral naltrexone among non-dependent binge-drinking MSM at risk for acquiring or transmitting HIV. Binge drinking (defined for men as drinking five or more drinks on one occasion), also known as heavy episodic drinking, is highly prevalent in the US. In 2010, the overall estimated prevalence of binge drinking (past 30 days) was 17%. Binge drinking accounts for more than half of the 80,000 annual deaths attributed to excessive alcohol consumption. In 2006, the economic costs of binge drinking exceeded $170 billion in the US. National HIV Behavioral Surveillance data indicate that 57% of men who have sex with men (MSM) reported binge drinking (past 30 days). Binge drinking among MSM has been independently associated with unprotected sex and HIV infection. Binge drinking is by far the most prevalent exposure attributed to HIV infections among MSM, who comprise over half of the 56,300 new HIV infections in the US in 2006. Thus, effective interventions to reduce binge drinking among MSM may function as an important HIV prevention intervention by reducing alcohol-related sexual risk behaviors. Despite the high prevalence of binge drinking and the continued domestic HIV epidemic among MSM, few alcohol interventions have been proven to be effective in this population. Oral naltrexone is a low-cost FDA-approved medication for alcohol dependence with few toxicities. Naltrexone is a �pioid receptor antagonist that attenuates the rewarding effects of alcohol. The standard daily regimen for oral naltrexone hampers compliance and alternate regimen schedules have been proposed to increase effectiveness of the drug and expand the population that may benefit from this pharmacologic intervention. One promising approach is the intermittent, targeted administration of naltrexone, whereby individuals take the medication as-needed, in anticipation of heavy drinking. Preliminary studies have observed that targeted naltrexone is efficacious in reducing heavy alcohol use, particularly for men. However, there have been no efficacy studies that have assessed targeted naltrexone among binge-drinking MSM and no trials aimed at reducing associated HIV risk behaviors. The aims of this study are to evaluate the efficacy of targeted naltrexone in binge-drinking MSM. Research Design: This is a double-blind, placebo-controlled trial of 120 binge-drinking MSM to 12 weeks of naltrexone 50mg, to be taken in anticipation of heavy drinking. Ethnically and racially diverse participants will be recruited using Respondent Driven Sampling. MSM will be seen weekly for alcohol-metabolite urine testing, study drug dispensing and brief counseling for alcohol use. Safety assessments and behavioral surveys will be completed monthly. Efficacy on alcohol consumption and alcohol-associated sexual risk behaviors (Aims 1-3) will be assessed using weekly time-line follow-back, screening for ethyl glucuronide (EtG)-positive urines, and computer administered monthly interventions. Tolerability and acceptability (Aim 4) will be assessed through tracking of adverse events and medication adherence. GEE models will be fitted to estimate treatment effects on repeated study outcomes.