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: 10095672
• 负责人: LARA A. RAY
• 金额: $ 8.36万
• 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/10095672
• 关键词: Alcohol consumption; Alcohols; Area; Clinical; Clinical Research; Clinical Trials; Cues; DSM-V; Detection; Development; Disease; Dose; 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; Testing; Titrations; Translations; Treatment Efficacy; United States; Visit; Woman; alcohol craving; alcohol cue; alcohol response; alcohol screening; alcohol use disorder; arm; breath alcohol measurement; clinically relevant; cost; cue reactivity; design; drinking; drinking behavior; improved; intrinsic motivation; men; novel; novel strategies; parent grant; phase 2 study; primary outcome; screening; smoking cessation; varenicline

Project Summary of Parent Grant: A Novel Human Laboratory Model for Screening Medications for Alcohol Use Disorder (R21AA027180) While developing novel medications to treat AUD remains a high research priority 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 the 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 propose to conduct a novel early efficacy detection paradigm informed by the smoking cessation medication development literature, to screen both an established (naltrexone) and a promising (varenicline) AUD medication. Specifically, this novel human laboratory protocol involves a randomized, double-blind, placebo-controlled, 3-arm parallel group design, in which individuals with current AUD reporting intrinsic motivation to change their drinking complete a week-long “practice quit attempt” and cue-reactivity paradigm. The primary outcome is the number of abstinent days during the practice quit week under active medication compared to placebo. The proposed laboratory protocol has been developed and validated for screening smoking cessation pharmacotherapies. The objective of this protocol is to adapt and validate this novel approach to screen pharmacotherapies for AUD.

父母资助项目总结：一种用于筛选药物的新型人类实验室模型 酒精使用障碍（R21AA027180） 虽然开发治疗AUD的新型药物仍然是一个高度优先的研究领域，但主要 有机会改进筛选新化合物的过程。为此，临床上的一个关键问题 研究新的化合物对AUD，是如何有效地确定一种新的药物是否有足够的 初步疗效的证据，以保证后续临床试验的进行。筛选小说的过程 用于初始功效的化合物，称为药物开发的早期阶段2，通常由以下组成： 人类实验室研究评估推定的临床相关性的结构，如酒精渴望， 对酒精的主观反应和实验室条件下的酒精自我给药。然而，尽管如此， 这些受控的人类实验室模型缺乏临床试验的生态有效性， 通过有动机改变其饮酒的个体中的临床意义的终点来确定效果。的 该提案的科学前提是，筛选新型AUD药物可以是有效的， 如果早期2期研究联合收割机将实验室测试的内部效度与 临床试验的外部效度。为此，我们建议进行一种新的早期疗效检测范式 通过了解戒烟药物开发文献，筛选既有 （纳洛酮）和一种有前途的（伐尼克兰）AUD药物。具体来说，这个新的人类实验室协议 涉及随机化、双盲、安慰剂对照、3臂平行组设计，其中， 当前AUD报告的改变饮酒的内在动机完成了为期一周的“实践戒烟尝试” 和线索反应范式。主要结果是在练习戒烟期间的禁欲天数 与安慰剂相比，活性药物治疗的周数。拟定的实验室方案已经制定， 并被验证用于筛选戒烟药物疗法。本协议的目的是适应 并验证这种新的方法来筛选AUD的药物治疗。