1/2-Multi-site Study: Varenicline Treatment of Alcohol Dependent Smokers

描述（由申请人提供）：这个提议的哥伦比亚大学和耶鲁大学合作项目的目的是测试伐尼克兰治疗酒精依赖的功效，这些人也报告每天吸烟。酒精依赖吸烟者的酒精中毒治疗效果较差，发病率和死亡率高于酒精依赖非吸烟者。吸烟和酒精依赖之间的强烈联系表明，共同的潜在因素可能为酒精和尼古丁使用提供治疗靶点。烟碱乙酰胆碱受体是尼古丁的主要作用靶点

DESCRIPTION (provided by applicant): The objective of this proposed Columbia-Yale collaborative project is to test the efficacy of varenicline for the treatment of alcohol dependenc among individuals who also report daily cigarette smoking. Alcohol dependent smokers have poorer alcoholism treatment outcomes and experience greater morbidity and mortality than alcohol dependent nonsmokers. The strong association between smoking and alcohol dependence suggests that common underlying factors may provide a therapeutic target for alcohol and nicotine use. Nicotinic acetylcholine receptors are the primary target of nicotine, and these receptors are involved in alcohol dependence. Varenicline is a partial nicotinic acetylcholine receptor antagonist with documented efficacy for smoking cessation. Varenicline also shows promise as a potential treatment for alcohol dependence based on preclinical models and recent human preliminary studies in heavy drinking smokers. Research conducted at Yale found that varenicline substantially reduces alcohol craving and drinking (compared to placebo) in a laboratory-alcohol administration paradigm and in a 3-week placebo controlled preliminary study. Based on these promising findings, the proposed study is a collaborative RO1 Phase II randomized double-blind placebo controlled 16-week study of varenicline for the treatment of alcohol drinking among 160 alcohol dependent daily smokers recruited at Yale and Columbia. The primary hypothesis is that varenicline will significantly reduce the percentage of heavy drinking days during the last two months of the treatment period. A secondary aim is to test the hypothesis that varenicline will promote smoking abstinence among alcohol dependent individuals who are not seeking smoking cessation counseling. Other secondary aims are to evaluate the effects of varenicline on alcohol and tobacco craving and the maintenance of change up through one-year. Finally, exploratory analyses will be conducted of moderators and mediators of varenicline effects. The combined recruitment resources and expertise of Yale and Columbia will advance the goals of the project. The potential benefits of varenicline, if confirmed, would represent a significant advance for the treatment of alcohol dependent smokers. PUBLIC HEALTH RELEVANCE: Alcohol dependent smokers have poorer alcoholism treatment outcomes and experience greater morbidity and mortality than alcohol dependent nonsmokers. Varenicline, which has documented efficacy for smoking cessation, also shows promise as a potential treatment for alcohol dependence based on preclinical models and recent human preliminary studies in heavy drinking smokers. The potential benefits of varenicline, if confirmed by our proposed study, would represent a significant advance for the treatment of alcohol dependent smokers.