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.

项目摘要/摘要 吸烟是美国可预防死亡的主要原因。鉴于复发 吸烟是任何给定退出尝试的最可能结果，迫切需要扩大治疗 烟草使用障碍（TUD）的选择，以改善持续的戒酒并防止吸烟复发。 临床前文献强调了谷氨酸在物质使用障碍中的作用，这表明新的目标是 药物治疗应集中于谷氨酸能功能的恢复。一种谷氨酸能剂 N-乙酰半胱氨酸（NAC）最近引起了极大的关注，这是一种安全且耐受性良好的药物 这已经显示出作为物质使用障碍的药物疗法的早期承诺，包括TUD。 初步临床研究表明，NAC的安全性，耐受性和潜在促进性 对几种虐待药物的禁欲。但是，随机临床试验的结果已混合在一起。作为 直到现在的NAC进行的TUD的药物疗法都仅限于试点研究，该研究 通常令人鼓舞，但也有些混杂。基于文献，知识的两个差距 关于TUD的NAC已经出现了：1）NAC在发起禁欲方面有效； 2）NAC有效 预防复发（或两者兼而有之）。该提议的R34将通过 评估NAC作为TUD的药物疗法。为了严格测试NAC的初始停止和 预防复发，参与者将有必要加强戒烟三天的戒烟 接受NAC（每天2400毫克）或匹配的安慰剂治疗。参与者将通过 呼吸碳一氧化碳（CO）样品每天远程取两次。经过三天的加固 禁欲，参与者将完成为期8周的治疗干预措施，他们将继续接受NAC 或安慰剂。这项研究将研究NAC与安慰剂相比的功效，以帮助吸烟者实现 连续节制三天（AIM＃1），检查8周干预的时间 在NAC和安慰剂组之间，在3天期间拒绝的人中（AIM＃2），并评估 为期8周的治疗研究访问（AIM＃3），在为期8周的治疗结束研究中禁欲为7天。结果将告知 治疗文献，并更好地了解如何最好地将NAC用作吸烟 药物疗法可为吸烟者带来最佳治疗结果。临床文献的混合结果 关于NAC的功效，从建议的应用中获得的知识至关重要。 在较大的随机对照试验中实施NAC或用于临床人群中。从中的发现 试验可能会产生明显的影响，因为NAC可以用作禁欲组合治疗的一部分 除了提供必要的初步数据外，有针对性的药物治疗或行为干预措施 用于TUD的NAC的全功率随机对照试验（R01）。