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

描述（由申请人提供）：为了响应RFA-RM-13-009，我们建议评估口服纳曲酮靶向剂量对有感染或传播艾滋病毒风险的非依赖性酗酒男男性行为者的疗效。酗酒（对男性的定义是一次喝五杯或五杯以上），也被称为重度间歇性饮酒，在美国非常普遍。2010年，狂饮（过去30天）的总体估计患病率为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，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）。男男性接触者的酗酒与无保护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感染艾滋病毒最普遍的原因，他们占2006年美国56,300例新感染艾滋病毒病例的一半以上。因此，通过减少与酒精相关的性风险行为，有效干预减少男男性行为者的酗酒行为可能是一项重要的艾滋病预防干预措施。尽管在男男性行为者中酗酒和持续的国内艾滋病毒流行率很高，但很少有酒精干预措施被证明对这一人群有效。口服纳曲酮是fda批准的治疗酒精依赖的低成本药物，毒性小。纳曲酮是一种类受体拮抗剂，可减弱酒精的有益作用。口服纳曲酮的标准每日方案阻碍了依从性，已经提出了替代方案时间表，以提高药物的有效性，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、有针对性地给药纳曲酮，即个人根据需要服用药物，预计会大量饮酒。初步研究已经观察到，靶向纳曲酮在减少大量饮酒方面是有效的，特别是对男性。然而，目前还没有针对纳曲酮对酗酒的男男性行为者的疗效研究，也没有针对减少相关艾滋病毒风险行为的试验。本研究的目的是评估靶向纳曲酮对酗酒的男男性行为者的疗效。研究设计：这是一项双盲、安慰剂对照试验，120名酗酒的男男性行为者服用了12周50毫克的纳曲酮，以预防酗酒。种族和种族多样化的参与者将使用受访者驱动抽样来招募。男男性行为者将每周接受酒精代谢物尿检，研究药物分配和简短的酒精使用咨询。每月完成安全评估和行为调查。对酒精消费和酒精相关的性危险行为的疗效（目标1-3）将通过每周时间线随访、筛查乙基葡萄糖醛酸盐（EtG）阳性尿液和计算机管理的每月干预来评估。耐受性和可接受性（目标4）将通过跟踪不良事件和药物依从性来评估。将拟合GEE模型来估计治疗对重复研究结果的影响。

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.