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：
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
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/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

项目摘要

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.

家长资助项目摘要：用于筛选药物的新型人体实验室模型酒精使用障碍 (R21AA027180) 虽然开发治疗 AUD 的新药物仍然是一个高度研究优先领域，但有一些主要的研究为此，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，筛选既定的戒烟药物（纳曲酮）和一种有前途的（伐尼克兰）AUD 药物，具体来说，是这种新颖的人体实验室方案。涉及随机、双盲、安慰剂对照、三臂平行组设计，其中患有当前澳元报告改变饮酒的内在动机完成为期一周的“练习戒烟尝试” 主要结果是戒烟期间的禁欲天数。与安慰剂相比，接受积极药物治疗的一周已制定了拟议的实验室方案。并经过验证用于筛选戒烟药物疗法。该方案的目的是适应。并验证这种筛选 AUD 药物疗法的新方法。