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

功效

• 批准号: 7797277
• 负责人: Peter Hauser
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 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 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797277
• 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; public health relevance; receptor; reduced alcohol use; standard of care

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: POTENTIAL IMPACT ON VETERANS HEALTH CARE: Effectively addressing alcohol use disorders in a hepatitis clinic will contribute to a new standard of care for HCV patients within the VA. This study has the potential to greatly reduce the number of veterans whose liver damage progresses to cirrhosis, hepatocellular carcinoma, and end stage liver disease that requires liver transplant or even more likely results in death (as many veterans who require liver transplant are rejected as candidates secondary to co-morbid alcohol/ substance use disorders). If baclofen is safe and efficacious in veterans with HCV, it has the potential to be used in the broader group of veterans with alcohol use disorders who do not have HCV. Also baclofen has the potential to be used by non-mental health care providers. Finally if we find that the results of this study are successful, we will use the already existing VA National Hepatitis C Resource Center infrastructure and communication network to disseminate our findings to all VA facilities in the US.

描述(由申请人提供)： 百氯芬在有丙型肝炎病毒背景的退伍军人中减少酒精使用的有效性和安全性：研究表明，在退伍军人事务医学中心(VAMCs)治疗的退伍军人中，慢性丙型肝炎(HCV)的患病率是普通人群1.8%患病率的3-4倍(Dominitz，2004；Cheung，2000)。相当大比例的携带丙型肝炎病毒的退伍军人有患上肝硬变和发展为终末期肝病的风险。携带丙型肝炎病毒的退伍军人有很高的共病酒精使用障碍的比率，酒精极大地加速了丙型肝炎病毒引起的肝脏损害。因此，对于患有丙型肝炎的退伍军人来说，需要一种安全有效的治疗酒精使用障碍的方法--一种不影响肝脏的治疗方法。巴氯芬是一种伽马氨基丁酸(GABA)β受体激动剂药物，FDA批准用于控制痉挛，最近也被证明对治疗肝硬变患者的酒精使用障碍有效(Addolorato，Agabio，Columbo和Gasbarrini，2006)。此外，巴氯芬的肝脏代谢率较低，主要通过肾脏消除(Davidoff，1985)。在对神经系统疾病或酒精使用障碍患者的研究中，没有报道巴氯芬对肝脏的副作用。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使用治疗方法，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。这项研究的目的和主要目的是确定在患有丙型肝炎和持续性酒精使用障碍的退伍军人中，与安慰剂相比，巴氯芬在减少酒精使用行为方面的有效性和安全性。这项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。计划/方法：这是一项多点随机、双盲、安慰剂对照研究。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的两个地点将招募120名丙型肝炎病毒阳性和目前正在饮酒的男性、女性和少数族裔退伍军人。参与者将接受酒精使用障碍的评估，如果他们符合酒精滥用或酒精依赖的标准，他们目前的酒精使用将被量化。符合中度到重度酒精使用标准的丙型肝炎退伍军人将被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，受试者将在为期4周的时间里每周接受一次检查，然后每2周接受一次检查，直到研究结束。在第12周，如果参与者是试验组(巴氯芬组)，则可以选择继续使用巴氯芬；如果他们是对照组(安慰剂组)，则可以选择开始使用巴氯芬。我们研究的主要结果将是比较两组退伍军人中实现和维持戒酒的丙型肝炎病毒携带者的比例。主要结果衡量标准将是完全戒酒的退伍军人人数、戒酒总天数和每周饮酒总数。在登记和研究结束时，将获得丙型肝炎病毒滴度，以确定戒酒或减少饮酒的效果。碳水化合物缺乏的转铁蛋白(%CDT)和乙基葡萄糖醛酸乙酯(EtG)将被用来评估戒酒或饮酒减少对这些措施的影响，这些措施将在研究登记时、第4周、第8周和研究结束时(第12周)获得。最后，将获得肝酶，以了解巴氯芬是否会对肝功能产生不利影响。临床意义：这项研究集中在VHA的最优先事项之一：治疗患有丙型肝炎病毒的退伍军人。大多数患有丙型肝炎病毒的退伍军人没有接受过抗病毒治疗，很大程度上是因为共病的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。这种药物既可以减缓酒精使用导致的肝病加速，又可以增加接受抗病毒治疗的可能性。因此，这项研究的相关性不仅在于其减少酒精使用和随之而来的加速肝损伤的潜力，还在于允许更多的丙型肝炎患者参与抗病毒治疗。 公共卫生相关性： 对退伍军人医疗保健的潜在影响：有效地解决肝炎诊所的酒精使用障碍将有助于在退伍军人管理局内为丙型肝炎患者提供新的护理标准。这项研究有可能极大地减少退伍军人的肝脏损伤进展为肝硬变、肝细胞癌和终末期肝病，需要肝移植甚至更有可能导致死亡的人数(因为许多需要肝移植的退伍军人被拒绝作为继发性酒精/药物使用障碍的候选人)。如果巴氯芬对感染丙型肝炎病毒的退伍军人是安全有效的，它有可能被用于更广泛的没有感染丙型肝炎病毒的酒精使用障碍退伍军人群体。此外，巴氯芬有可能被非精神卫生保健提供者使用。最后，如果我们发现这项研究的结果是成功的，我们将利用已经存在的退伍军人管理局国家丙型肝炎资源中心的基础设施和通信网络将我们的发现传播到美国的所有退伍军人管理局。