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(定义为男性一次喝五杯或五杯以上的饮料)与严重的发病率和死亡率有关。在美国，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，冰毒和酗酒的流行率分别是普通美国成年人的20倍和3.5倍。此外，这两种物质一直与无保护措施的性行为和MSM中的艾滋病毒血清转换有关，MSM占美国新增感染人数的一半以上。因此，减少冰毒使用和酗酒的有效干预措施也可能通过减少与物质相关的艾滋病毒风险行为而发挥重要的艾滋病毒预防战略的作用。纳曲酮是一种U-阿片受体拮抗剂，是治疗吸毒和酗酒的MSM的有前途的药物。纳曲酮已显示出减少苯丙胺复发的效果，并已获得FDA批准用于酒精依赖。口服纳曲酮价格低廉，毒性很小，但纳曲酮的标准每日治疗方案存在问题，因为患者忘记了服药。考虑到每日给药的挑战，已经提出了替代方案时间表，以提高疗效并扩大可能受益的人口。一种方法是间歇性靶向给药，即个体在预期药物使用或渴望期间根据需要服用药物。在接触安非他明之前给予纳曲酮可显著减轻饥饿感，靶向纳曲酮已显示出减少重度酒精使用的效果。然而，还没有研究评估在使用冰毒和酗酒的MSM中间歇性靶向剂量的纳曲酮。多物质使用模式在MSM中很常见--迫切需要对服用一种以上物质的人进行研究。这项研究的目的是确定在非依赖使用冰毒和酗酒的MSM中，靶向剂量的纳曲酮是否可行、耐受和可接受。设计：这是一项定向口服纳曲酮的先导性、双盲、安慰剂对照试验。30名非依赖型、间歇性使用冰毒和酗酒的MSM将被随机分配接受8周的纳曲酮50毫克或安慰剂治疗，根据需要服用纳曲酮，以缓解冰毒欲望或减少酗酒。参与者将每两周接受一次学习药物和物质使用咨询。安全评估和行为调查将在每两周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)将通过登记和保留率、不良事件的频率、参与者对靶向剂量和用药依从性的评估来评估。将通过每日短信和每两周一次的时间线追踪(探索性目标)来评估冰毒使用和饮酒结果。性行为将通过每月调查(探索性目标)进行评估。GEE Logistic模型将用于比较MSM在冰毒渴求和酗酒期间服药的比例。吉二项和负二项模型将用于评估冰毒使用、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.