EVarQuit: Extinguishing cigarette smoking via extended pre-quit varenicline

项目摘要/摘要 Varenicline是现有的最有效的戒烟疗法。然而，大多数人 使用varenicline的吸烟者在戒烟后的头几个月内会复发。伐伦克林是 假设部分通过减少吸烟的强化效应来帮助吸烟者戒烟 在标准的1周戒烟前治疗阶段。学习理论与前人 动物研究支持这一假设，即较长持续时间的伐伦克林治疗在 到目标戒烟日期(TQD)将使每个人吸烟的数量减少更多 戒烟前一天，与标准的varenicline相比，长期戒断率更高 治疗。在我们有希望的初步临床数据的基础上，我们建议测试这些 一项全面随机临床试验(RCT)的假设。四百人次就诊 吸烟者(200名女性)将被随机分成标准磨合组(服用3周的安慰剂， 然后是标准的TQD前1周的Varenicline)或延长磨合组(4周 TQD前的varenicline)。两组都将接受短暂的个人戒烟咨询，并将接受11 TQD后数周的Varenicline。主要的结果衡量标准将是生物验证的连续 在治疗结束(戒烟后8-11周)和长期随访(8-26周)时戒酒 和辞职后的8-52)。假设的中介机制(例如，吸烟强化)将是 通过融合行为、生理和主观测量进行评估 实验室和使用真实世界的实时电子瞬时评估(EMA)。我们预测 长期的生物验证戒烟将在延长磨合组中得到改善 与标准磨合组相比。我们进一步预测临床结果的改善 延长磨合的varenicline将通过更大的退出前减少来解释(或调解) 延长磨合组与标准磨合组的吸烟强化效果比较 一群人。这项工作的意义是明确的：我们的目标是提供最佳的治疗方法 戒烟更好，使用一种成熟的推广方法和方法 这将阐明下一代治疗靶向的关键机制 增强功能。

PROJECT SUMMARY/ABSTRACT Varenicline is the most effective smoking cessation therapy available. Nevertheless, most smokers using varenicline relapse within the first few months after quitting. Varenicline is hypothesized to help smokers to quit in part by reducing the reinforcing effects of smoking during the standard 1-week pre-quitting treatment phase. Learning theory and previous human and animal research support the hypothesis that a longer duration of varenicline treatment prior to the target quit date (TQD) will yield greater decreases in the number of cigarettes smoked per day before quitting, and higher long-term cessation rates, compared to standard varenicline treatment. Building on our promising preliminary clinical data, we propose to test these hypotheses with a full-scale randomized clinical trial (RCT). Four hundred treatment-seeking smokers (200 female) will be randomized to a standard run-in group (3 weeks of placebo, followed by the standard 1 week of pre-TQD varenicline) or an extended run-in group (4 weeks of pre-TQD varenicline). Both groups will receive brief individual cessation counseling and 11 weeks of post-TQD varenicline. The primary outcome measure will be bio-verified continuous abstinence at end-of-treatment (weeks 8-11 post-quit) and at long-term follow-up (weeks 8-26 and 8-52 post-quit). Hypothesized mediating mechanisms (e.g., smoking reinforcement) will be evaluated by converging behavioral, physiological, and subjective measures assessed both in the lab and using real-world, real-time electronic momentary assessments (EMA). We predict that long-term, bio-verified smoking cessation will be improved among the extended run-in group compared to the standard run-in group. We further predict the improved clinical outcomes with extended run-in varenicline will be explained (or mediated) by greater pre-quit reductions in smoking reinforcement among the extended run-in group compared to the standard run-in group. The significance of this work is clear: We aim to make best available treatment for smoking cessation even better, using a method that is ripe for dissemination and an approach that will elucidate critical mechanisms to target in the next generation of treatment enhancement.