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

1/2 多中心研究：伐尼克兰治疗酒精依赖型吸烟者

• 批准号: 8617200
• 负责人: STEPHANIE S O'MALLEY
• 金额: $ 56.83万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-05 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8617200
• 关键词: Abstinence; Address; Aftercare; Alcohol consumption; Alcohol dependence; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Attenuated; Behavior Therapy; Biochemical; Biological; Biological Assay; Cigarette; Cigarette Smoker; Clinical Trials; Cotinine; Counseling; Cues; Data; Dopamine; Double-Blind Method; Eligibility Determination; Ethanol; Evaluation; FDA approved; Genetic; Glucuronides; Goals; Heavy Drinking; Human; Individual; Industry; Intervention; Laboratories; Maintenance; Measures; Mediator of activation protein; Monitor; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Nicotine; Nicotine Dependence; Nicotinic Receptors; Participant; Patient Self-Report; Pharmacotherapy; Pharmacy facility; Phase; Placebo Control; Placebos; Population; Pre-Clinical Model; Quality Control; Randomized; Recruitment Activity; Refractory; Reporting; Research; Resources; Safety; Sample Size; Site; Site Visit; Smoker; Smoking; Teleconferences; Testing; Tobacco; Training; Treatment outcome; United States National Institutes of Health; Urine; Work; acetylcholine receptor agonist; alcohol abuse therapy; alcohol craving; alcoholism therapy; base; cigarette smoking; clinical care; craving; data management; drinking; efficacy testing; experience; follow-up; meetings; mortality; non-smoker; placebo controlled study; pre-clinical research; receptor; response; secondary outcome; smoking cessation; therapeutic target; treatment duration; varenicline; web site

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.

描述（由申请人提供）：该拟议的哥伦比亚-耶鲁合作项目的目的是测试伐尼克兰治疗每天吸烟的个体的酒精依赖的功效。与酒精依赖的非吸烟者相比，酒精依赖的吸烟者的酒精中毒治疗结果较差，发病率和死亡率更高。吸烟和酒精依赖之间的密切关联表明，常见的潜在因素可能为酒精和尼古丁的使用提供治疗目标。烟碱乙酰胆碱受体是尼古丁的主要靶标， 这些受体与酒精依赖有关。 Varenicline 是一种部分烟碱乙酰胆碱受体拮抗剂，具有戒烟功效。根据临床前模型和最近对重度饮酒吸烟者的人体初步研究，伐尼克兰还显示出作为酒精依赖的潜在治疗方法的前景。耶鲁大学进行的研究发现，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，伐尼克兰显着降低了对酒精的渴望和饮酒（与安慰剂相比）。基于这些有希望的发现，拟议的研究是一项协作性 RO1 II 期随机双盲安慰剂对照研究，为期 16 周，在耶鲁大学和哥伦比亚大学招募了 160 名依赖酒精的每日吸烟者，使用伐尼克兰治疗饮酒。主要假设是伐尼克兰将显着降低治疗期最后两个月的酗酒天数百分比。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。其他次要目标是评估伐尼克兰对酒精和烟草渴望的影响以及一年内维持变化的效果。最后，将对伐尼克兰效应的调节因素和调节因素进行探索性分析。耶鲁大学和哥伦比亚大学的招聘资源和专业知识的结合将推进该项目的目标。伐尼克兰的潜在益处如果得到证实，将代表着治疗酒精依赖型吸烟者的重大进步。