Combining varenicline and naltrexone for smoking cessation and drinking reduction

 描述(由申请人提供)：吸烟和饮酒之间有很强的正相关性。据估计，目前约有20%-25%的吸烟者也是酗酒者。更多的饮酒与戒烟几率降低有关，据估计，吸烟者在饮酒期间经历吸烟失误的可能性是吸烟者的4倍。尽管有这些数据，但没有针对酗酒吸烟者的可用治疗方法，吸烟者是一个相当大的抗药性亚群。这项建议试图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VAR单独(每天两次1毫克)，NTX单独(每天50毫克)，以及联合VAR(每天两次1毫克)+NTX(每天一次50毫克)，用于戒烟和减少酒精使用的样本每天大量饮酒的吸烟者(即每天吸烟=10支并符合NIAAA重度饮酒指南的个人)。PI最近完成了一项非治疗寻求大量饮酒的实验室试验，发现在实验室饮酒和吸烟期间，VAR+NTX的组合在减轻尼古丁和酒精引起的奖赏方面优于单一疗法和安慰剂。此外，与安慰剂相比，联合用药组在积极用药期间显著减少了香烟和酒精的消耗。基于我们人体实验室试验的初步证据，这项建议通过测试VAR和NTX在重度饮酒吸烟者中的联合戒烟作用，将这些发现扩展到寻求治疗的人群。总共411名寻求治疗的重度饮酒吸烟者将被随机分为(1)VAR组，(2)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别咨询，并将在戒烟日之前完成实验室测试。通过一氧化碳(CO)水平和饮酒量验证的戒烟情况将在戒烟日期后2、8、12、16和26周进行测量。这项研究将测试VAR+NTX在2周、8周、12周、16周和26周时是否比单一疗法导致更高的吸烟率。它还将检查药物对酒精使用的影响。第二个目标是通过检查尼古丁和酒精反应的实验室标记物作为治疗结果的预测因素来测试药物治疗反应的机制。在我们之前工作的基础上，这些目标将阐明在酗酒和戒烟的吸烟者中，VAR+NTX的组合比单一疗法更好。

 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.