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

The Better THAN 研究：纳曲酮针对 MSM 中的重度酒精

• 批准号: 9264381
• 负责人: Glenn-Milo Santos
• 金额: $ 19.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-19 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264381
• 关键词: Better; THAN; Study; Targeting; Heavy

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.

描述（由申请方提供）：作为对RFA-RM-13-009的回应，我们建议在有感染或传播HIV风险的非依赖性酗酒MSM中评价口服纳洛酮靶向给药的疗效。酗酒（定义为男性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，酗酒（过去30天）的总体估计流行率为17%。在每年因过量饮酒而死亡的8万人中，酗酒占一半以上。2006年，美国酗酒的经济成本超过1700亿美元。国家艾滋病毒行为监测数据表明，57%的男男性行为者报告酗酒（过去30天）。男男性行为者的酗酒与无保护性行为和艾滋病毒感染独立相关。到目前为止，酗酒是男男性行为者中最普遍的艾滋病毒感染，2006年美国56，300例新艾滋病毒感染者中有一半以上是男男性行为者。因此，有效的干预措施，以减少酗酒的男男性接触者可能会作为一个重要的艾滋病预防干预措施，减少与酒精有关的性风险行为。尽管酗酒的高流行率和持续的国内艾滋病毒流行的男男性行为者，酒精干预措施已被证明是有效的，在这一人群。口服纳洛酮是一种低成本的FDA批准的酒精依赖药物，几乎没有毒性。纳洛酮是一种类阿片受体拮抗剂，可减弱酒精的奖励作用。口服纳洛酮的标准每日方案阻碍了依从性，已提出替代方案时间表以增加药物的有效性并扩大可能从这种药理学干预中受益的人群。一种有希望的方法是间歇性的，有针对性的给药纳洛酮，即个人根据需要服用药物，预计大量饮酒。初步研究已经观察到，靶向纳洛酮在减少重度酒精使用方面是有效的，特别是对于男性。然而，目前还没有针对性的纳洛酮在酗酒的男男性行为者中的疗效研究，也没有旨在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洛酮在酗酒MSM中的疗效。研究设计：这是一项双盲、安慰剂对照试验，120名狂饮MSM接受为期12周的纳洛酮50 mg，以预防重度饮酒。将使用受访者驱动抽样招募种族和种族多样化的参与者。MSM将每周接受酒精代谢物尿液检测、研究药物分发和酒精使用简短咨询。安全评估和行为调查将每月完成。将使用每周时间线随访、筛查乙基葡糖苷酸（EtG）阳性尿液和计算机管理的每月干预措施，评估对饮酒和酒精相关性风险行为（目的1-3）的疗效。将通过跟踪不良事件和药物依从性来评估耐受性和可接受性（目标4）。将拟合GEE模型，以估计重复研究结局的治疗效应。