A Novel Human Laboratory Model for Screening Medications for Alcohol Use Disorder

用于筛选酒精使用障碍药物的新型人体实验室模型

• 批准号: 10019310
• 负责人: LARA A. RAY
• 金额: $ 18.53万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019310
• 关键词: Alcohol consumption; Alcohols; Area; Clinical; Clinical Research; Clinical Trials; Cross-Over Studies; Crossover Design; Cues; DSM-V; Detection; Development; Disease; Double-Blind Method; FDA approved; Human; Individual; Laboratories; Laboratory Study; Literature; Methods; Modeling; Naltrexone; Outcome; Participant; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebos; Procedures; Process; Protocols documentation; Randomized; Reading; Reporting; Research Priority; Self Administration; Signal Transduction; Testing; Translations; Treatment Efficacy; United States; Woman; alcohol craving; alcohol cue; alcohol response; alcohol screening; alcohol use disorder; breath alcohol measurement; clinically relevant; cost; cue reactivity; drinking; drinking behavior; improved; intrinsic motivation; men; novel; novel strategies; phase 2 study; phase 2 testing; primary outcome; screening; smoking cessation

ABSTRACT While developing novel medications to treat AUD remains a high priority research area, there are major opportunities to refine the process of screening novel compounds. To that end, a key question in clinical studies of novel compounds for AUD, is how to efficiently determine whether a novel medication has sufficient evidence of initial efficacy to warrant the conduct of subsequent clinical trials. The process of screening novel compounds for initial efficacy, known as the early phase 2 of medications development, often consists of human laboratory studies assessing constructs of putative clinical relevance, such as alcohol craving, subjective response to alcohol, and alcohol self-administration under laboratory conditions. Nevertheless, these controlled human laboratory models lack the ecological validity of clinical trials in which medication effects are established via clinically meaningful endpoints in individuals motivated to change their drinking. The scientific premise of this proposal is that screening novel AUD medications can be efficient and clinically meaningful if early phase 2 studies combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, we proposed to conduct a novel early efficacy detection paradigm informed by the smoking cessation medication development literature, to screen a promising AUD medication. Specifically, this novel human laboratory protocol involves a placebo-controlled, within-subjects, crossover design, in which individuals with current AUD reporting intrinsic motivation to change their drinking complete two week-long “practice quit attempts” and cue-reactivity paradigm separated by a 1 week washout period. The primary outcome is the number of abstinent days during each practice quit week. The proposed laboratory protocol has been developed and validated for screening smoking cessation pharmacotherapies. The objective of this proposal is to adapt and validate this novel approach to screen pharmacotherapies for AUD.

抽象的 虽然开发治疗 AUD 的新药物仍然是一个高度优先的研究领域，但有一些主要的研究领域 改进筛选新化合物的过程的机会。为此，临床上的一个关键问题 对 AUD 新型化合物的研究，是如何有效地确定一种新型药物是否具有足够的 初步疗效的证据，以保证进行后续临床试验。小说筛选流程 具有初始疗效的化合物，称为药物开发的早期 2 阶段，通常包括 人类实验室研究评估假定的临床相关性的结构，例如对酒精的渴望， 对酒精的主观反应以及实验室条件下的酒精自我管理。尽管如此， 这些受控人体实验室模型缺乏临床试验的生态有效性，其中药物治疗 效果是通过对有动力改变饮酒的个体进行具有临床意义的终点来确定的。这 该提案的科学前提是筛选新型 AUD 药物可以有效且符合临床 如果早期 2 期研究将实验实验室测试的内部有效性与 临床试验的外部有效性。为此，我们建议进行一种新颖的早期功效检测范例 根据戒烟药物开发文献，筛选有前途的 AUD 药物。 具体来说，这种新颖的人类实验室方案涉及安慰剂控制的受试者内交叉 设计，其中当前澳元的个人报告改变其饮酒习惯的内在动机 为期两周的“练习戒烟尝试”和提示反应范式，中间间隔 1 周的冲洗期。这 主要结果是每个戒烟练习周的戒烟天数。拟建实验室 已经制定并验证了筛查戒烟药物疗法的方案。目标 该提案的目的是调整和验证这种筛选 AUD 药物疗法的新方法。