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.

巴氯芬减少HCV感染退伍军人饮酒的有效性和安全性 背景：研究表明，慢性丙型肝炎（HCV）的患病率在退伍军人治疗内， 退伍军人事务医疗中心（VAMC）的患病率是普通人群的3至4倍 1.8%（Dominitz，2004; Cheung，2000）。很大一部分患有HCV的退伍军人有肝硬化的风险 并发展为终末期肝病患有HCV的退伍军人有很高的并发症酒精使用率 疾病和酒精大大加速了HCV引起的肝损伤。因此，安全有效的 对于患有HCV的退伍军人，需要治疗酒精使用障碍--一种不影响肝脏的疾病。 巴氯芬，一种γ-氨基丁酸（GABA）β受体激动剂药物，经FDA批准， 控制痉挛，最近也被证明是有效的治疗酒精使用障碍， 肝硬化患者（Addolorato，Agabio，科隆博，& Gasbarrini，2006）。此外，巴氯芬具有低的 肝脏代谢，主要通过肾脏未经修饰地消除（Daviberg，1985）。有 在神经系统疾病或饮酒患者的研究中，没有报告巴氯芬的肝脏副作用 紊乱在慢性HCV感染患者中，尚未研究有效的酒精使用治疗方法 目前FDA批准的酒精使用障碍药物会对肝脏产生不利影响。目的 本研究的主要目的是确定巴氯芬在减少饮酒方面的有效性和安全性 在患有HCV和持续性酒精使用障碍的退伍军人中与安慰剂相比的行为。一 本研究的第二个目的是评估巴氯芬在减少酒精渴望方面的有效性。 方法：这是一项多中心随机双盲安慰剂对照研究。两个网站的 位于明尼阿波利斯和波特兰VAMC的国家VA丙型肝炎资源中心将招募120名男性， 妇女和少数民族退伍军人谁是丙型肝炎病毒阳性，目前饮酒。参与者将被 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， 目前的酒精使用将被量化。符合中度至重度饮酒标准的HCV退伍军人 将被随机分配到两组之一：实验组（巴氯芬）或对照组（安慰剂）。 参与者将接受12周的治疗。在此期间，受试者将每周接受一次访视，持续4周，然后 每2周一次，直至研究结束。在第12周，参与者将被给予继续巴氯芬的选择 如果他们在实验组（巴氯芬）或开始巴氯芬，如果他们在对照组（安慰剂） 组我们研究的主要结果将是两组之间的比例比较， 达到并保持戒酒的HCV退伍军人。主要结果指标将是 完全戒酒的退伍军人人数，戒酒的总天数，以及每名退伍军人的饮酒总数。 周在入组时和研究结束时，将获得HCV病毒滴度，以确定 戒酒或减少饮酒。碳水化合物缺乏转铁蛋白（%CDT）和乙基葡糖苷酸的百分比 (EtG)将用于评估戒酒或减少饮酒对这些措施的影响，这些措施将 在入组研究时、在第4周、在第8周和在研究结束时（第12周）获得。最后是肝脏 将获得酶，以评估巴氯芬是否对肝功能产生不利影响。 临床相关性：这项研究的重点之一VHA的最高优先事项：治疗退伍军人与 HCV。大多数患有HCV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。目前没有研究 评估药物在减少HCV患者饮酒方面的安全性和有效性。此类药物 既可以减缓酒精使用引起的肝脏疾病的加速， 抗病毒治疗因此，这项研究的相关性不仅在于它有可能减少酒精的使用， 这不仅可以加速肝损伤，而且可以使更多的HCV患者参与抗病毒治疗。