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

基本信息

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
项目类别：
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

项目摘要

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为此，有机会改进筛选新化合物的过程，这是临床中的一个关键问题。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保证进行后续临床试验的初步疗效证据。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，对酒精的反应，以及实验室条件下酒精的主观自我管理。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机改变饮酒的个体进行具有临床意义的终点来确定的。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为此，我们建议进行一种新颖的早期疗效检测范例。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饮酒行为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。主要结果是每个戒烟实践周的戒烟天数。已制定并验证了筛选戒烟药物疗法的方案。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。