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.

抽象的 青春期是酗酒问题发展的关键时期，大约 15% 符合酒精使用障碍 (AUD) 标准的 18 岁青少年。治疗青少年 AUD 的努力仅 效果中等，高达 86% 的青少年在治疗后 12 个月内恢复使用。不足 鉴于青少年时期饮酒的比例很高，因此对青少年的治疗是一个重要的公共卫生问题 预测长期饮酒问题。虽然有几种药物可以有效治疗成人 AUD， 最低限度的药物治疗研究主要集中在青少年。评估替代方案和更有效的方案 对患有 AUD 的青少年进行治疗是有必要的。拟议的第二阶段证明的主要目标是 概念研究旨在评估 N-乙酰半胱氨酸 (NAC) 与安慰剂相比在减少酒精摄入方面的效果 在患有 AUD 的寻求治疗的青少年中使用（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及性、青少年的安全性和耐受性， 而且成本低廉，这种药物作为青少年 AUD 的潜在治疗选择具有广阔的前景。在 响应国家酒精滥用和酒精中毒研究所加速研究的倡议 为了开发 AUD 的有效药物治疗方法，我们将 (1) 进行为期 8 周的意向治疗， NAC（每天 2400 毫克）的双盲、平行组、随机、安慰剂对照试验； (2)检查 在基线、整个治疗过程中以及治疗后对临床结果进行标准化、重复的依赖性测量 治疗随访； (3) 采用移动技术来改善数据收集、参与和药物治疗 坚持。确定一种耐受性良好、有效的药物治疗方法将代表 重大进展，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 评估 NAC 作为青少年 AUD 的药物疗法，并且不考虑 NAC 与安慰剂的结果 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 青少年澳元。