Combining varenicline and naltrexone for smoking cessation and drinking reduction

 描述（由申请人提供）：吸烟和饮酒之间存在强烈的正相关。据估计，目前大约有20-25%的吸烟者也是酗酒者。更多的酒精使用与戒烟的几率降低有关，据估计，吸烟者在饮酒期间经历吸烟中断的可能性要高出4倍。尽管有这些数据，但没有针对大量饮酒吸烟者的治疗方法，这是一个相当大的和治疗抵抗的亚组。本提案旨在通过进行双盲、随机临床试验来解决文献中的这一空白 使用三组药物设计，包括单独的VAR（1 mg，每日两次）、单独的NTX（50 mg，每日一次）和VAR（1 mg，每日两次）+ NTX（50 mg，每日一次）的组合，用于在大量饮酒的每日吸烟者样本中戒烟和减少酒精使用（即，PI最近完成了一项非寻求重度饮酒治疗的实验室试验，该试验发现VAR + NTX的组合在减弱实验室中酒精和香烟施用期间尼古丁和酒精诱导的奖赏方面上级单一疗法和安慰剂。此外，与安慰剂相比，联合用药组在活性药物治疗期间显著减少了吸烟和饮酒。基于我们人体实验室试验的初步证据，该提案通过测试VAR和NTX联合用于重度饮酒吸烟者戒烟，将这些发现扩展到寻求治疗的人群。共411例寻求治疗的重度饮酒吸烟者将随机分配至（1）仅VAR组、（2）仅NTX组或（3）VAR + NTX组。药物将在14天内滴定，所有参与者将接受吸烟和饮酒的个人咨询，并将在戒烟日之前完成实验室测试。在戒烟日期后第2、8、12、16和26周，通过一氧化碳（CO）水平和饮酒量验证戒烟情况。本研究将测试VAR + NTX是否导致第2、8、12、16和26周的戒烟率高于单药治疗。它还将研究药物对酒精使用的影响。次要目的是通过检查尼古丁和酒精反应的实验室标志物作为治疗结果的预测因子来测试药物治疗反应的机制。基于我们以前的工作，这些目标将阐明VAR + NTX联合治疗在重度饮酒吸烟者的酒精使用和戒烟方面上级单药治疗。

 DESCRIPTION (provided by applicant): There is a strong positive association between cigarette smoking and alcohol use. It is estimated that approximately 20-25% of current smokers are also heavy drinkers. Greater alcohol use is associated with decreased odds of smoking cessation and it is estimated that smokers are 4 times more likely to experience a smoking lapse during drinking episodes. Despite these data, there are no available treatments tailored to heavy drinking smokers, a sizeable and treatment-resistant sub-group. This proposal seeks to address this gap in the literature by conducting a double-blind, randomized clinical trial using three group medication design consisting of VAR alone (1 mg twice daily), NTX alone ( 50 mg once daily), and the combination of VAR (1 mg twice daily) + NTX (50 mg once daily) for smoking cessation and alcohol use reduction in a sample of heavy drinking daily smokers (i.e., individuals who smoke = 10 cigarettes/day and who meet NIAAA guidelines for heavy drinking).The PI has recently completed a laboratory trial with non-treatment seeking heavy drinking which found that the combination of VAR + NTX was superior to monotherapy and to placebo in attenuating nicotine- and alcohol-induced reward during alcohol and cigarette administration in the lab. Further, the combination group significantly reduced cigarette and alcohol consumption during the active medication period, as compared to placebo. Based on the preliminary evidence from our human laboratory trial, this proposal extends these findings to treatment seeking populations by testing the combination of VAR and NTX for smoking cessation among heavy drinking smokers. A total of 411 treatment-seeking heavy drinking smokers will be randomized to (1) VAR only, (2) NTX only, or (3) VAR + NTX. Medication will be titrated over a 14-day period and all participants will receive individual counseling for smoking and drinking and will complete the laboratory testing session prior to the quit day. Smoking abstinence, verified by carbon monoxide (CO) levels and alcohol consumption will be measured at 2, 8, 12, 16, and 26 weeks after quit date. This study will test whether VAR + NTX result in higher rates of point prevalence smoking abstinence at 2, 8, 12, 16, and 26 weeks compared to monotherapy. It will also examine the effects of medication on alcohol use. The secondary aims are to test mechanisms of pharmacotherapy response by examining laboratory markers of nicotine and alcohol response as predictors of treatment outcome. Building upon our previous work, these aims will elucidate the combination of VAR + NTX is superior to monotherapy for alcohol use and smoking cessation in heavy drinking smokers.