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

描述(由申请者提供)：哥伦比亚大学和耶鲁大学合作项目的目标是测试varenicline对每天吸烟的人的酒精依赖的治疗效果。与酒精依赖非吸烟者相比，酒精依赖吸烟者的酒精中毒治疗结果更差，发病率和死亡率更高。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的使用提供了一个治疗靶点。尼古丁的主要靶标是烟碱型乙酰胆碱受体，以及 这些受体与酒精依赖有关。Varenicline是一种部分烟碱型乙酰胆碱受体拮抗剂，已有文献证明其戒烟效果。根据临床前模型和最近对酗酒吸烟者的初步研究，varenicline也显示出作为酒精依赖的潜在治疗方法的前景。在耶鲁大学进行的研究发现，在实验室酒精管理范例和为期3周的安慰剂对照初步研究中，varenicline大大减少了酒精渴望和饮酒(与安慰剂相比)。基于这些有希望的发现，这项拟议的研究是一项合作的RO1阶段II随机双盲安慰剂对照研究，为期16周，用于治疗耶鲁大学和哥伦比亚大学招募的160名酒精依赖每日吸烟者的酒精饮酒。主要的假设是，在治疗期的最后两个月，varenicline将显著减少重度饮酒天数的百分比。第二个目的是验证这样的假设，即varenicline将在没有寻求戒烟咨询的酒精依赖者中促进戒烟。其他次要目标是评估varenicline对酒精和烟草欲望的影响，并通过一年的时间保持变化。最后，将对Varenicline效应的调节剂和调节剂进行探索性分析。耶鲁大学和哥伦比亚大学的联合招聘资源和专业知识将推进该项目的目标。如果得到证实，varenicline的潜在好处将代表着治疗酒精依赖吸烟者的显著进步。

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.