Ho Diana, Towns Brandon, Grodin Erica N, Ray Lara A
Department of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
Trials. 2020 Nov 23;21(1):947. doi: 10.1186/s13063-020-04842-w.
Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline.
Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long "practice quit attempt" while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions.
The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials.
ClinicalTrials.gov NCT04249882 . Registered on 31 January 2020.
酒精使用障碍（AUD）在美国是一种高度流行的慢性复发性疾病，疾病负担沉重。药物治疗是治疗AUD的一种有前景的方法；然而，美国食品药品监督管理局（FDA）批准的药物数量有限，且效果一般。AUD的药物研发是一个高度优先的研究领域，但繁琐的药物研发过程阻碍了许多潜在化合物获得批准。一个有重大改进机会的领域是筛选新化合物初始疗效的过程，即早期2期试验。早期2期试验采用人体实验室范式来评估相关临床指标，如对酒精的渴望和主观反应。然而，这些对照范式往往缺乏临床试验的生态效度。因此，如果早期2期试验将实验实验室测试的内部效度与临床试验的外部效度相结合，可能会更高效且具有临床意义。为此，本研究旨在借鉴戒烟文献，开发并验证一种新的早期疗效范式，用于筛选治疗AUD的新药物。作为一种已获批的治疗AUD的药物，纳曲酮将作为活性对照，以测试实践戒烟尝试模型以及一种有前景的治疗AUD的药物伐尼克兰的疗效。
目前患有AUD且表示有内在动力改变饮酒习惯的个体，在服用研究药物期间将完成为期一周的“实践戒烟尝试”。参与者被随机分组并设盲，分别服用纳曲酮、伐尼克兰或安慰剂。在实践戒烟尝试期间，参与者将通过电话完成每日访视，并填写关于饮酒、对酒精的渴望和情绪的在线问卷。此外，参与者将接受两次酒精线索反应测试。
本研究的成功完成将通过提出并验证一种用于筛选治疗AUD药物疗法的新早期疗效模型来推进药物研发，这反过来可作为一种有效策略，用于决定是否继续进行临床试验的取舍决策。
ClinicalTrials.gov NCT04249882。于2020年1月31日注册。
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