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
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.