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

功效

• 批准号: 8206291
• 负责人: Peter Hauser
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206291
• 关键词: Abstinence; Acceleration; Address; Adherence; Adverse effects; Affect; Agonist; Alanine Transaminase; Albumins; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Antiviral Agents; Antiviral Therapy; Appointment; Aspartate Transaminase; Baclofen; Behavior; Bilirubin; Blood Urea Nitrogen; Cessation of life; Chronic Hepatitis C; Cirrhosis; Clinic; Clinic Visits; Communication; Creatinine; Double-Blind Method; Effectiveness; Enrollment; Enzymes; FDA approved; General Population; Glucuronides; Health Personnel; Healthcare; Heavy Drinking; Hepatic; Hepatitis; Hepatitis C; Hepatitis C virus; Kidney; Liver; Liver Function Tests; Liver diseases; Measures; Medical center; Minority; Outcome Measure; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Prevalence; Primary carcinoma of the liver cells; Randomized; Recruitment Activity; Reporting; Research Infrastructure; Resources; Risk; Safety; Sampling; Secondary to; Site; Staging; Substance Use Disorder; Time; Veterans; Viral; Woman; alcohol abstinence; alcohol craving; alcohol use disorder; carbohydrate-deficient transferrin; craving; drinking; effective therapy; gamma-Aminobutyric Acid; liver function; liver metabolism; liver transplantation; meetings; men; nervous system disorder; placebo controlled study; primary outcome; receptor; reduced alcohol use; standard of care

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.

Baclofen的功效和安全性减少HCV退伍军人的酒精含量 背景：研究表明，在接受治疗的退伍军人中，慢性丙型肝炎（HCV）的患病率 退伍军人事务中心（VAMCS）比普通人口大3到4倍 1.8％（Dominitz，2004； Cheung，2000）。 HCV的退伍军人很大一部分有肝硬化的风险 并发展为末期肝病。 HCV的退伍军人合并饮酒率很高 疾病和酒精会大大加速HCV造成的肝脏损害。因此，安全有效的 患有HCV的退伍军人需要对酒精使用障碍的治疗 - 一种不影响肝脏的治疗。 Baclofen，一种γ-氨基丁酸（GABA）β受体激动剂药物，该药物已批准为FDA 对照痉挛，最近还显示出在治疗酒精使用障碍中有效 肝硬化患者（Addolorato，Agabio，Colombo和Gasbarrini，2006年）。此外，巴氯芬的低 肝脏代谢，主要通过肾脏被消除（Davidoff，1985）。有 在神经系统疾病或饮酒的患者研究中，巴氯芬尚无肝副作用 疾病。在长期感染HCV的患者中，尚未研究有效的饮酒治疗方法 当前的FDA批准药物用于饮酒障碍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含量方面的功效和安全性 与具有HCV和持续酒精使用障碍的退伍军人的安慰剂相比。一个 这项研究的次要目的是评估巴氯芬在减少酒精渴望中的有效性。 计划/方法：这是一项多站点随机的双盲安慰剂对照研究。两个站点 位于明尼阿波利斯和波特兰VAMCS的国家VA乙型肝炎资源中心将招募120名男子 HCV阳性且目前饮酒的妇女和少数退伍军人。参与者会 评估饮酒障碍，如果它们符合酗酒或酒精依赖的标准 当前的酒精使用将被量化。有HCV的退伍军人，符合中度至大量酒精的标准 将随机分配给两个组之一：实验组（Baclofen）或对照组（安慰剂）。 参与者将接受12周的治疗。在此期间，受试者每周将在4周内看到。 每2周，直到研究结束。在第12周，将为参与者选择继续巴氯芬 如果它们在实验（巴氯芬）组中或启动baclofen，如果它们在对照中（安慰剂） 团体。我们研究的主要结果将是比较这两组的比较 拥有HCV的退伍军人，他们实现并维持戒酒。主要结果措施将是 保证总数，戒酒的总数和每次饮料总数 星期。在入学后和研究结束时，将获得HCV病毒滴度，以确定 禁欲或减少饮酒。碳水化合物不足的转铁蛋白（％CDT）和乙基葡萄糖醛酸乙酯百分比 （ETG）将用于评估禁欲或饮酒对这些措施的影响，这将是 在第4周，第8周和研究结束时（第12周）在研究后获得研究。终于肝 将获得酶，以获取巴氯芬是否不利影响肝功能。 临床相关性：本研究重点介绍VHA的最高优先事项之一：对退伍军人的处理 HCV。大多数具有HCV的退伍军人尚未接受抗病毒疗法治疗，这在很大程度上是因为 病态的酒精使用障碍被认为是抗病毒疗法的障碍。目前没有研究 评估药物在减少HCV患者饮酒方面的安全性和功效。这样的药物 既可以减慢饮酒引起的肝病的加速度，又可能增加接受的可能性 抗病毒疗法。因此，这项研究的相关性不仅在于减少饮酒的潜力和 因此，加速了肝脏损害，但也使更多的HCV患者参与抗病毒疗法。