A Proof-of-Concept Trial of N-Acetylcysteine for Adolescent Alcohol Use Disorder

N-乙酰半胱氨酸治疗青少年酒精使用障碍的概念验证试验

• 批准号: 10241372
• 负责人: Kevin M Gray
• 金额: $ 72.5万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-22 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241372
• 关键词: 18 year old; Abstinence; Acetylcysteine; Addictive Behavior; Adherence; Adolescence; Adolescent; Adult; Aftercare; Age; Agreement; Alcohol abuse; Alcohol consumption; Alcohols; Antioxidants; Back; Behavior; Biological; Biological Markers; Clinical Trials; Coupled; Data; Data Collection; Development; Double-Blind Method; Evaluation; Event; Future; Glucuronides; Glutamates; Healthcare Systems; Heavy Drinking; Homeostasis; Measures; Methodology; Methods; Mind; Monitor; National Institute on Alcohol Abuse and Alcoholism; Outcome; Patient Self-Report; Pattern; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Phase; Placebos; Procedures; Public Health; Randomized Controlled Trials; Research; Resistance; Safety; Self Administration; Societies; Standardization; Substance Use Disorder; System; Testing; Time; TimeLine; Treatment Efficacy; Youth; addiction; adolescent alcohol treatment; adolescents with alcohol use disorders; adverse outcome; age group; alcohol use disorder; alcohol use initiation; base; brief alcohol intervention; carbohydrate-deficient transferrin; clinical outcome measures; cost; design; drinking; effective therapy; efficacious treatment; efficacy outcomes; efficacy trial; evidence base; follow-up; improved; marijuana use disorder; medication compliance; meetings; mobile computing; phase III trial; phosphatidylethanol; pill; preclinical study; prevent; randomized placebo controlled trial; reduced alcohol use; response; therapy development; underage drinking

ABSTRACT Adolescence marks a key period in the development of problematic alcohol use, with approximately 15% of 18 year olds meeting criteria for alcohol use disorder (AUD). Efforts to treat adolescent AUD have been only modestly effective, with up to 86% of youth returning to use within 12 months following treatment. Inadequate treatment for adolescents is an important public health concern given that alcohol use during this time is highly predictive of long-term problematic drinking. While several medications are efficacious in treating adult AUD, minimal pharmacotherapy research has focused on adolescents. Evaluation of alternative and more efficacious treatments for adolescents with AUD is warranted. The primary objective of the proposed Phase II proof-of- concept study is to evaluate the effect of N-acetylcysteine ( NAC), compared to placebo, in reducing alcohol use among treatment-seeking adolescents with AUD (N=120). Given NAC’s effect on addictive behaviors via glutamate modulation, accessibility as an over-the-counter supplement, safety and tolerability with adolescents, and low cost, this medication holds great promise as a potential treatment option for adolescents with AUD. In response to the National Institute on Alcohol Abuse and Alcoholism’s initiative to accelerate research on the development of effective pharmacologic treatments for AUD, we will (1) conduct an 8-week, intent-to-treat, double-blind, parallel-group, randomized, placebo-controlled trial of NAC (2400 mg per day); (2) examine standardized, repeated dependent measures of clinical outcomes at baseline, throughout treatment, and at post- treatment follow-up; and (3) employ mobile technology to improve data collection, engagement, and medication adherence. The identification of a well-tolerated, effective pharmacological treatment would represent a significant advance and could yield tremendous public health impact. The proposed trial will provide critical data to evaluate NAC as a pharmacotherapy for adolescent AUD, and regardless of NAC versus placebo outcomes will provide key methodological guidance for future randomized controlled trials of pharmacotherapies for adolescent AUD.

摘要 青少年是酒精使用问题发展的关键时期，大约15%的青少年 符合酒精使用障碍（AUD）标准的18岁青奥尔兹。治疗青少年AUD的努力仅限于 适度有效，高达86%的青少年在治疗后12个月内恢复使用。不足 青少年的治疗是一个重要的公共卫生问题，因为在这段时间内饮酒是非常重要的。 这预示着长期酗酒。虽然几种药物在治疗成人AUD中是有效的， 最低限度的药物治疗研究集中在青少年身上。评价替代方案，更有效 青少年AUD的治疗是必要的。第二阶段的主要目标是： 一项概念性研究是评估N-乙酰半胱氨酸（NAC）与安慰剂相比在减少饮酒方面的作用 在寻求治疗的AUD青少年中使用（N=120）。鉴于NAC对成瘾行为的影响， 谷氨酸调节，作为非处方补充剂的可获得性，青少年的安全性和耐受性， 而且成本低，这种药物作为青少年AUD的潜在治疗选择具有很大的希望。在 对国家酒精滥用和酒精中毒研究所关于加速研究酒精滥用和酒精中毒的倡议的回应 为了开发有效的AUD药物治疗，我们将（1）进行为期8周的意向治疗， NAC（2400 mg/d）的双盲、平行组、随机、安慰剂对照试验;（2）检查 在基线、整个治疗期间和治疗后， 治疗随访;（3）采用移动的技术来改善数据收集、参与和用药 坚持。确定一种耐受性良好、有效的药物治疗将代表 这是一项重大进步，可能产生巨大的公共卫生影响。拟议的试验将提供关键数据 评价NAC作为青少年AUD的药物治疗，不考虑NAC与安慰剂的结局 将为未来的药物治疗随机对照试验提供关键的方法学指导， 青少年AUD