Evaluating N-acetylcysteine as a pharmacotherapy for tobacco use disorder

评估 N-乙酰半胱氨酸作为烟草使用障碍的药物疗法

• 批准号: 9302369
• 负责人: Erin A McClure
• 金额: $ 21.91万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9302369
• 关键词: Abstinence; Acetylcysteine; Address; Animal Model; Attention; Behavior Therapy; Carbon Monoxide; Cessation of life; Chronic; Cigarette Smoker; Clinical; Clinical Research; Data; Development; Drug Exposure; Drug usage; Ensure; Evidence based treatment; Glutamatergic Agents; Glutamates; Intervention; Investigation; Knowledge; Literature; Modeling; Outcome; Participant; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Placebos; Population; Prevalence; Randomized Clinical Trials; Randomized Controlled Trials; Relapse; Research; Role; Safety; Sampling; Smoker; Smoking; Substance Use Disorder; Substance of Abuse; Testing; Time; Tobacco Use Disorder; Treatment outcome; United States; Visit; Work; base; cigarette smoking; disorder later incidence prevention; drug of abuse; evidence base; experimental study; functional restoration; glutamatergic signaling; improved; new therapeutic target; pre-clinical; prevent; restoration; smoking cessation; therapy development

Project Summary/Abstract Cigarette smoking is the leading cause of preventable death in the United States. Given that relapse to smoking is the most likely outcome of any given quit attempt, there is a pressing need to expand treatment options for tobacco use disorder (TUD) to improve sustained abstinence and prevent relapse to smoking. Preclinical literature highlights the role of glutamate in substance use disorders, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. One glutamatergic agent that has garnered significant attention recently is N-acetylcysteine (NAC), which is a safe and well tolerated medication that has shown early promise as a pharmacotherapy for substance use disorders broadly, including TUD. Preliminary clinical studies have demonstrated NAC's safety, tolerability, and potential efficacy for promoting abstinence from several drugs of abuse. However, results from randomized clinical trials have been mixed. As a pharmacotherapy for TUD, work conducted with NAC up to this point has been limited to pilot studies, which have been generally encouraging, but also somewhat mixed. Based on the literature, two gaps in knowledge regarding NAC for TUD have emerged: 1) is NAC effective in initiating abstinence; and 2) is NAC effective for relapse prevention, following a period of abstinence (or both). This proposed R34 will address these gaps by evaluating NAC as a pharmacotherapy for TUD. In order to rigorously test NAC for both initial cessation and relapse prevention, participants will be contingently reinforced for abstinence from smoking for three days while undergoing NAC (2400 mg per day) or matched placebo treatment. Participants will verify abstinence through breath carbon monoxide (CO) samples taken remotely twice per day. Following three days of reinforced abstinence, participants will complete an 8-week treatment intervention, in which they will continue to take NAC or placebo. This study will examine the efficacy of NAC, compared to placebo, in helping smokers achieve three days of continuous abstinence (Aim #1), examine the time to relapse over the 8-week intervention between NAC and placebo groups, among those who were abstinent for the 3-day period (Aim #2), and assess 7-day point prevalence abstinence at the 8-week end-of-treatment study visit (Aim #3). Results will inform the treatment literature and provide a better understanding of how NAC is best used as a smoking cessation pharmacotherapy to achieve the best treatment outcomes for smokers. Mixed results from the clinical literature on NAC's efficacy suggest that the knowledge to be gained from the proposed application is essential prior to implementing NAC in larger randomized controlled trials or for use in a clinical population. Findings from this trial may have notable impact, as NAC could be used as part of combination treatment with abstinence- targeted pharmacotherapies or behavioral interventions, in addition to providing the preliminary data necessary for a fully-powered randomized controlled trial (R01) of NAC for TUD.

项目总结/摘要 吸烟是美国可预防死亡的主要原因。考虑到你的旧病复发 吸烟是任何戒烟尝试最可能的结果，迫切需要扩大治疗范围。 烟草使用障碍（TUD）的选择，以改善持续戒烟和预防复吸。 临床前文献强调了谷氨酸在物质使用障碍中的作用，表明谷氨酸的新靶点 药物治疗应侧重于恢复神经功能。一种能产生放射性物质的物质 最近引起广泛关注的是N-乙酰半胱氨酸（NAC），这是一种安全且耐受性良好的药物 其已经显示出作为广泛物质使用障碍包括TUD的药物疗法的早期前景。 初步的临床研究已经证明了NAC的安全性，耐受性和促进肿瘤生长的潜在功效。 戒除几种滥用药物。然而，随机临床试验的结果好坏参半。作为 作为TUD的药物疗法，迄今为止，NAC的研究仅限于试点研究， 总的来说是令人鼓舞的，但也有些好坏参半。根据文献，两个知识空白 关于NAC治疗TUD的问题：1）NAC是否有效启动禁欲; 2）NAC是否有效治疗TUD？ 预防复发，在一段时间的禁欲（或两者兼而有之）。拟议的R34将通过以下方式解决这些差距： 评估NAC作为TUD的药物疗法。为了严格测试NAC的初始停止和 预防复吸，参与者将被紧急加强戒烟三天， 接受NAC（2400 mg/天）或匹配的安慰剂治疗。参与者将通过以下方式验证禁欲 每天两次远程采集呼吸一氧化碳（CO）样本。经过三天的强化 禁欲，参与者将完成为期8周的治疗干预，在此期间，他们将继续服用NAC 或安慰剂。这项研究将检查NAC与安慰剂相比在帮助吸烟者实现 连续戒断3天（目标1），检查8周干预期间复发的时间 NAC和安慰剂组之间，在禁欲3天的患者中（目标#2），并评估 7-8周治疗结束研究访视时的日点戒烟率（目标3）。结果将通知 治疗文献，并更好地了解NAC如何最好地用于戒烟 药物治疗，以达到最佳的治疗效果的吸烟者。临床文献的混合结果 的功效表明，从拟议的应用程序中获得的知识是必不可少的， 在较大的随机对照试验中实施NAC或用于临床人群。时发现的问题 试验可能会产生显着的影响，因为NAC可以用作与禁欲联合治疗的一部分- 有针对性的药物治疗或行为干预，除了提供必要的初步数据 一项NAC治疗TUD的全把握度随机对照试验（R 01）。