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

描述（由申请人提供）：该拟议的哥伦比亚-耶鲁大学合作项目的目的是测试伐尼克兰治疗每日吸烟的酒精依赖者的疗效。酒精依赖的吸烟者比酒精依赖的非吸烟者有更差的酒精中毒治疗结果和更高的发病率和死亡率。吸烟和酒精依赖之间的强相关性表明，共同的潜在因素可能为酒精和尼古丁的使用提供治疗靶点。尼古丁乙酰胆碱受体是尼古丁的主要靶点， 这些受体与酒精依赖有关。伐尼克兰是一种部分烟碱乙酰胆碱受体拮抗剂，有戒烟疗效的记录。基于临床前模型和最近在重度饮酒吸烟者中的人类初步研究，伐尼克兰也显示出作为酒精依赖的潜在治疗的希望。在耶鲁大学进行的研究发现，伐尼克兰在实验室酒精管理模式和为期3周的安慰剂对照初步研究中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，拟议的研究是一个合作的RO 1 II期随机双盲安慰剂对照16周的研究伐尼克兰治疗饮酒160酒精依赖的每日吸烟者招募在耶鲁大学和哥伦比亚。主要假设是伐尼克兰将显著降低治疗期最后两个月期间重度饮酒天数的百分比。第二个目的是检验伐尼克兰将促进不寻求戒烟咨询的酒精依赖者戒烟的假设。其他次要目的是评估伐尼克兰对酒精和烟草渴望的影响，以及在一年内保持变化的情况。最后，将对伐尼克兰效应的调节剂和介导剂进行探索性分析。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动该项目的目标。伐尼克兰的潜在益处如果得到证实，将代表酒精依赖吸烟者治疗的重大进展。

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.