Selegiline Patch for Treatment of Nicotine Dependence

用于治疗尼古丁依赖的司来吉兰贴剂

• 批准号: 6806539
• 负责人: JOEL D KILLEN
• 金额: $ 56.78万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806539
• 关键词: biological signal transduction; body composition; carbon monoxide; clinical research; clinical trials; craving; deprenyl; depression; dopamine receptor; dopamine transporter; drug abuse chemotherapy; drug withdrawal; genetic mapping; genetic polymorphism; genotype; human subject; human therapy evaluation; nicotine replacement; patient oriented research; relapse /recurrence; serotonin transporter; smoking; smoking cessation; tobacco abuse

DESCRIPTION (provided by applicant): 350 adult smokers will be enrolled in the study. Primary aim: To conduct the first randomized controlled trial of the efficacy of selegiline patch (STS) for the treatment of nicotine dependence. We propose that STS will promote more durable treatment effects by alleviating craving and other withdrawal symptoms that emerge following nicotine deprivation and have the effect of promoting relapse. Our primary hypothesis is that smokers randomized to receive STS will have a higher prolonged abstinence rate (PA) at 6-month follow-up than those who receive matching placebo. PA at 6 months will be the outcome measure used to evaluate the primary hypothesis. PA is defined as a report of non-smoking following an initial 2-week grace period during which any smoking is not counted as a failure and an expired-air carbon monoxide level of <9PPM. With 175 participants per cell we will have at least 80 percent power at alpha of .05 to detect a difference in abstinence rates of at least 10 -15 percent across a range of success probabilities. Secondary obiectives: we propose to genotype all subjects for polymorphisms at loci hypothesized to affect nicotine dependence and/or selegiline efficacy. These include the serotonin transporter, the dopamine transporter, dopamine D2 receptor, and the dopamine Dpercent receptor. Analyses will examine whether polymorphisms at these loci moderate response to treatment. The proposed study will address several important gaps in our knowledge of effective smoking cessation treatment. First, this will be the first RCT to examine the efficacy of selegiline patch for the treatment of nicotine dependence. Second, this study will be one of the first, if not the first, prospective trial of smoking cessation techniques in which genetic data are included as predictors of outcome. Third, we plan to conduct mediation and moderation analyses to explore factors that may influence response to treatment. The study will provide important practical information to the medical and health communities concerning the utility of selegiline for smoking cessation and will advance our knowledge of the underlying relationship of nicotine addiction and depression.

描述（由申请人提供）：研究将参加350名成年吸烟者。主要目的：进行塞莱吉林贴片（STS）治疗尼古丁依赖性的第一个随机对照试验。我们建议STS通过减轻尼古丁剥夺后出现的渴望和其他戒断症状来促进更耐用的治疗效果，并具有促进复发的作用。我们的主要假设是，在6个月的随访中，随机接收STS的吸烟者的戒酒率（PA）比接受匹配的安慰剂的持续时间更高。 6个月时的PA将是用于评估主要假设的结果指标。 PA被定义为在最初的2周宽限期之后不吸烟的报告，在此期间，任何吸烟都不被视为失败，而过期的空气一氧化碳水平为<9ppm。每个细胞的参与者有175个参与者，我们在α上至少有80％的功率为.05，以检测一系列成功概率的节制率至少为10-15％。次要构型：我们提出基因型的所有受试者，以影响尼古丁的依赖性和/或塞勒吉林疗效。这些包括5-羟色胺转运蛋白，多巴胺转运蛋白，多巴胺D2受体和多巴胺dpercent受体。分析将检查这些基因座对治疗的中等反应的多态性。拟议的研究将解决我们对有效戒烟治疗的知识中的几个重要差距。首先，这将是第一个检查塞勒吉林斑块对尼古丁依赖性治疗的功效的RCT。其次，这项研究将是吸烟技术的第一个（即使不是第一次）前瞻性试验之一，其中包括遗传数据作为预后的预测指标。第三，我们计划进行调解和适度分析，以探索可能影响治疗反应的因素。这项研究将向医学和健康社区提供有关塞莱吉林在戒烟的效用的重要实际信息，并将促进我们对尼古丁成瘾和抑郁症之间基本关系的了解。