Harm reduction with pharmacotherapy for homeless adults with alcohol dependence

描述(申请人提供)：无家可归和酒精依赖是常见的和严重的公共卫生问题。不幸的是，基于禁欲的酒精治疗方法在参与并成功治疗有酒精依赖的无家可归者方面效果甚微。因此，人们呼吁采取更灵活、更以客户为中心的方法，以满足这一群体的需求。创新、低障碍的方法(例如，住房优先和酒精管理计划)已经应用于这一人群，在减少酒精使用和相关问题以及利用公共资助的服务和相关成本方面是有效的。这种方法被称为减少伤害干预措施，因为它们侧重于减少与酒精有关的对受影响个人及其社区的伤害，而不需要承诺实现以禁欲为基础的目标。尽管心理社会、减少伤害的方法开始对这一人群激增，但很少有药理学同行支持和加强这些努力。一种可以弥补这一治疗缺口的药物是缓释纳曲酮(XR-NTX；市场名称为Vivitrol(R))。XR-NTX是阿片受体拮抗剂纳曲酮的30天缓释制剂，每月通过臀部肌肉注射给药。拟议的第二阶段研究以四臂随机对照试验(N=300)为特色，旨在测试XR-NTX作为社区机构为酒精依赖无家可归者提供的现有减少心理社会伤害服务的药理附件的有效性。这项拟议的研究将包括24周的随访，并将测试3种积极治疗组合--1)XR-NTX减少伤害咨询、2)安慰剂减少伤害咨询和3)仅减少伤害咨询(HRC)--与所有参与者从社区机构获得的照常服务(TAU)相比较的相对效果。这一拟议的设计将允许我们拆除主动治疗组件，从而检测注射管理和医疗关注的潜在“安慰剂效应” 很专业。在本研究中，主要有三个具体目标。首先，我们将测试XR-NTX、安慰剂和HRC与TAU相比在减少酒精数量、频率和酒精相关问题方面的相对有效性。其次，我们将检验干预效果的假设调解人。具体地说，我们假设积极的治疗将促使改变动机的增加和渴望的减少，这反过来将中介积极治疗对酒精结果的影响。最后，我们将测试公共资助服务成本(即紧急医疗服务、急诊室就诊、入院和县监狱)的治疗效果。据推测，XR-NTX、安慰剂和HRC组在公共资助的服务成本方面的降幅将比TAU组更大。

DESCRIPTION (provided by applicant): Homelessness and alcohol dependence are commonly co-occurring and serious public health issues. Unfortunately, abstinence-based alcohol treatment approaches are minimally effective in engaging and successfully treating homeless individuals with alcohol dependence. There have therefore been calls for more flexible and client-centered approaches tailored to this population's needs. Innovative, low-barrier approaches (e.g., Housing First and alcohol management programs) have been applied with this population and are efficacious in reducing alcohol use and related problems as well as utilization of publicly funded services and associated costs. Such approaches have been referred to as harm-reduction interventions because they focus on reducing alcohol-related harm for affected individuals and their communities without requiring a commitment to abstinence-based goals. Although psychosocial, harm-reduction approaches are beginning to proliferate for this population, there are few pharmacological counterparts to support and enhance these efforts. One medication that could address this treatment gap is extended-release naltrexone (XR-NTX; marketed as Vivitrol(R)). XR-NTX is a 30-day, extended release formulation of the opioid receptor antagonist, naltrexone, and is administered monthly via gluteal intramuscular injection. The proposed Phase II study features a four- arm RCT (N=300) designed to test the efficacy of XR-NTX as a pharmacological adjunct to existing psychosocial harm-reduction services provided by community agencies to homeless people with alcohol dependence. The proposed study will include a 24-week follow-up and will test the relative efficacy of 3 active treatment combinations-1) XR-NTX+harm reduction counseling, 2) placebo+harm reduction counseling and 3) harm reduction counseling only (HRC)-compared to the services as usual (TAU) that all participants receive from community agencies. This proposed design will allow us to dismantle active treatment components and thereby detect potential "placebo effects" of both the administration of an injection and attention from a medical professional. In this study, there are three primary specific aims. First, we will test the relativ efficacy of XR-NTX, placebo and HRC compared to TAU in decreasing alcohol quantity, frequency and alcohol-related problems. Second, we will test hypothesized mediators of the intervention effects. Specifically, we hypothesize that the active treatments will precipitate increases in motivation to change and decreases in craving, which, in turn, will mediate the active treatment effects on alcohol outcomes. Finally, we will test treatment effects on publicly funded service costs (i.e., emergency medical services, ER visits, hospital admissions, and county jail). It is hypothesized that XR-NTX, placebo and HRC groups will show greater decreases in publicly funded service costs than the TAU group.