Efficacy & safety of baclofen to reduce alcohol use in veterans with HCV

百氯芬减少丙型肝炎病毒感染退伍军人酒精使用的疗效和安全性 背景：研究表明，在退伍军人中接受治疗的人中慢性丙型肝炎的患病率 退伍军人事务医疗中心(VAMCs)的患病率是普通人群的3到4倍 1.8%(Dominitz，2004；Cheung，2000)。携带丙型肝炎病毒的退伍军人中有相当一部分有患上肝硬变的风险。 并进展为终末期肝病。携带丙型肝炎病毒的退伍军人有很高的共病饮酒率 疾病和酒精极大地加速了丙型肝炎病毒对肝脏的损伤。因此，一种安全有效的 患有丙型肝炎的退伍军人需要治疗酒精使用障碍-一种不会影响肝脏的治疗方法。 巴氯芬，一种伽马氨基丁酸(GABA)β受体激动剂药物，FDA批准 控制痉挛，最近也被证明在治疗酒精使用障碍方面有效 肝硬变患者(Addolorato、Agabio、科伦坡和Gasbarrini，2006)。此外，巴氯芬具有较低的 肝脏代谢，主要通过肾脏消除(Davidoff，1985)。曾经有过 在神经系统疾病或酒精使用患者的研究中，巴氯芬没有肝脏副作用的报道 精神错乱。在慢性感染丙型肝炎病毒的患者中，还没有研究有效的酒精治疗方法。 目前FDA批准的治疗酒精使用障碍的药物可能会对肝脏产生不利影响。目的 这项研究的主要目的是确定巴氯芬在减少酒精使用方面的有效性和安全性 患有丙型肝炎和持续性酒精使用障碍的退伍军人的行为与安慰剂的比较。一个 这项研究的第二个目的是评估巴氯芬在减少酒精渴求方面的有效性。 计划/方法：这是一项多点随机、双盲、安慰剂对照研究。的两个地点 位于明尼阿波利斯和波特兰的国家退伍军人管理局丙型肝炎资源中心将招募120名男性， 女性，以及目前正在饮酒的丙型肝炎病毒阳性的少数族裔退伍军人。参与者将是 评估酒精使用障碍，如果他们符合酒精滥用或酒精依赖的标准，他们的 目前的酒精使用量将被量化。符合中度到重度酒精使用标准的丙型肝炎病毒退伍军人 将随机分配到两组中的一组：试验组(巴氯芬)或对照组(安慰剂)。 参与者将接受为期12周的治疗。在此期间，受试者将每周接受一次探视，为期4周 每2周进行一次，直到研究结束。在第12周，参与者将可以选择继续服用巴氯芬 如果他们是试验组(巴氯芬组)，或者如果他们是对照组(安慰剂)，则开始使用巴氯芬组 一群人。我们研究的主要结果将是比较两组之间的比例 实现并保持戒酒的丙型肝炎病毒感染退伍军人。主要结果衡量标准将是 完全戒酒的退伍军人人数、戒酒总天数和每年饮酒总数 星期。在登记时和研究结束时，将获得丙型肝炎病毒滴度，以确定 禁酒或减少饮酒。缺糖转铁蛋白(%CDT)和乙基葡萄糖醛酸苷 (ETG)将用于评估戒酒或减少饮酒对这些措施的影响，这将是 在研究登记时、第4周、第8周和研究结束时(第12周)获得。最后是肝脏 将获得酶以了解巴氯芬是否会对肝功能产生不利影响。 临床相关性：这项研究集中在VHA的最优先事项之一：治疗退伍军人 丙型肝炎。大多数患有丙型肝炎的退伍军人没有接受过抗病毒治疗，这在很大程度上是因为... 病态酒精使用障碍被认为是抗病毒治疗的禁忌症。目前还没有研究 评估药物在减少丙型肝炎患者酒精使用方面的安全性和有效性。这样的药物 既可以减缓饮酒引起的肝脏疾病的加速，又可以增加接受 抗病毒治疗。因此，这项研究的相关性不仅在于其减少酒精使用的潜力，而且还在于 因此加速了肝损害，但也允许更多的丙型肝炎患者参与抗病毒治疗。

Efficacy & Safety of Baclofen to Reduce Alcohol Use in Veterans with HCV BACKGROUND: Studies suggest the prevalence of chronic hepatitis C (HCV) among veterans treated within the Veterans Affairs Medical Centers (VAMCs) is 3 to 4 times greater than the general population prevalence of 1.8% (Dominitz, 2004; Cheung, 2000). A substantial proportion of veterans with HCV are at risk for cirrhosis and progression to end-stage liver disease. Veterans with HCV have high rates of co-morbid alcohol use disorders and alcohol accelerates greatly the liver damage caused by HCV. Therefore, a safe and efficacious treatment for alcohol use disorders-one that does not affect the liver- is needed for veterans with HCV. Baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist medication that is FDA approved to control spasticity, more recently has also been shown to be effective in treating alcohol use disorders in patients with cirrhosis (Addolorato, Agabio, Colombo, & Gasbarrini, 2006). Furthermore, baclofen has a low liver metabolism and is mainly eliminated unmodified through the kidneys (Davidoff, 1985). There have been no hepatic side effects reported for baclofen in studies of patients with neurological disorders or alcohol use disorders. Effective treatments for alcohol use have not been studied in patients chronically infected with HCV and current FDA-approved medications for alcohol use disorders can adversely affect the liver. The purpose and primary aim of this study is to determine the efficacy and safety of Baclofen in reducing alcohol use behavior as compared with placebo in veterans who have HCV and persistent alcohol use disorders. A secondary aim of this study is to assess the effectiveness of Baclofen in reducing alcohol craving. PLAN/ METHODS: This is a multi-site randomized double-blind placebo controlled study. Two sites of the national VA Hepatitis C Resource Center located at the Minneapolis and Portland VAMCs will recruit 120 men, women, and minority veterans who are HCV positive and currently drinking alcohol. Participants will be assessed for alcohol use disorders and, if they meet criteria for alcohol abuse or alcohol dependence, their current alcohol use will be quantified. Veterans with HCV who meet criteria for moderate to heavy alcohol use will be randomly assigned to one of two groups: Experimental group (baclofen) or control (placebo). Participants will be treated for 12 weeks. During this period subjects will be seen weekly for 4 weeks then every 2 weeks until the end of the study. At week 12,participants will be given the option of continuing baclofen if they were in the experimental (baclofen) group or starting baclofen if they were in the control (placebo) group. The primary outcome of our study will be a comparison between the two groups of the proportion of veterans with HCV who achieve and maintain alcohol abstinence. Primary outcome measures will be the number of veterans with total abstinence, the total number of days abstinent, and the total number of drinks per week. Upon enrollment and at the end of the study HCV viral titers will be obtained to determine the effect of abstinence or drinking reduction. A Percent Carbohydrate Deficient Transferrin (%CDT) and Ethyl Glucuronide (EtG) will be used to assess the effect of abstinence or drinking reduction on these measures, which will be obtained upon enrollment to the study, at week 4, at week 8 and at the end of the study (week 12). Finally liver enzymes will be obtained in order to access whether Baclofen adversely affects liver function. CLINICAL RELEVANCE: This study focuses on one of VHA's highest priorities: treatment of veterans with HCV. A majority of veterans with HCV have not been treated with antiviral therapy, in large part because co- morbid alcohol use disorders are considered a contra-indication to antiviral therapy. Currently no studies evaluate the safety and efficacy of medications in reducing alcohol use in patients with HCV. Such medication could both slow the acceleration of liver disease caused by alcohol use and increase the likelihood of receiving antiviral therapy. Therefore this study's relevance lies not only in its potential to reduce alcohol use and the consequent accelerated liver damage but also in allowing more HCV patients to participate in antiviral therapy.