Intermittent Naltrexone among Polysubstance Users

描述（由申请人提供）：甲基苯丙胺（冰毒）使用和酗酒（男性定义为一次喝五杯或五杯以上）与显著的发病率和死亡率相关。在美国，冰毒使用和酗酒的经济成本分别超过230亿美元和1700亿美元。在男男性行为者中，冰毒使用和酗酒的流行率分别是美国普通成年人的20倍和3.5倍。此外，这两种物质始终与男男性行为者之间的无保护性行为和艾滋病毒血清转化相关，男男性行为者占美国新感染者的一半以上。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，作为一种重要的艾滋病毒预防策略。纳洛酮是一种u阿片受体拮抗剂，是一种很有前途的治疗吸毒和酗酒MSM的药物。纳洛酮已显示出减少苯丙胺类药物复发的疗效，并被FDA批准用于酒精依赖。口服纳洛酮价格便宜，毒性小，但纳洛酮的标准每日方案是有问题的，因为患者忘记服用药物。鉴于每日给药的挑战，已提出替代方案时间表以提高疗效并扩大可能受益的人群。一种方法是间歇性靶向给予纳洛酮，即个人在预期物质使用或渴望期间根据需要服用药物。在暴露于安非他明之前给予纳洛酮显著减弱了渴望，并且靶向纳洛酮在减少重度酒精使用方面显示出功效。然而，目前还没有研究评估间歇性靶向剂量的纳洛酮之间的甲基使用和酗酒的男男性接触者。多物质使用模式在MSM中很常见，迫切需要对那些服用多种物质的人进行研究。本研究的目的是确定纳洛酮的靶向给药是否是可行的，耐受性和可接受的非依赖性的甲基使用和酗酒的男男性接触者。设计：这是一项靶向口服纳洛酮的先导性、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MSM将被随机分配接受8周的纳洛酮50 mg或安慰剂，根据需要服用，以减轻冰毒的渴望或减少酗酒。受试者将每两周接受一次研究药物和物质使用咨询。安全性评估和行为调查将在每两周和每月访视时完成。可行性、耐受性和可接受性（特定目标1-3）将通过入组率和保留率、不良事件频率、受试者对目标剂量和药物依从性的评价进行评估。将通过每日短信和每两周一次的时间轴随访（探索性目的）评估甲氧西林使用和饮酒结果。将通过每月调查（探索性目标）评估性行为。将使用GEE逻辑模型比较在冰毒渴望和狂饮期间服用药物的MSM的比例。GEE二项和负二项模型将用于评估对甲基苯丙胺使用，饮酒和性行为的治疗效果。 公共卫生相关性：在男男性行为者（MSM）中，使用冰毒和酗酒与艾滋病毒相关的性风险行为和艾滋病毒感染有关。本研究将探讨在MSM对冰毒的渴望期间和预期饮酒期间按需服用纳洛酮的可行性、耐受性和可接受性。这项研究将有助于边缘化和不成比例的影响人口的物质使用和艾滋病毒预防研究领域。

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.