A novel human laboratory model for screening medications for alcohol use disorder.
A novel human laboratory model for screening medications for alcohol use disorder.
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DOI：
10.1186/s13063-020-04842-w
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发表时间：
2020-11-23
期刊：
影响因子：
2.5
通讯作者：
Ray LA
中科院分区：
文献类型：
--
作者：
Ho D;Towns B;Grodin EN;Ray LA
酒精使用障碍(AUD)在美国是一种高度流行的慢性复发性障碍，疾病负担很高。药物疗法是一种很有前途的治疗AUD的方法；然而，FDA批准的少数药物仅具有适度的疗效。治疗AUD的药物开发是一个高度优先的研究领域，但繁琐的药物开发过程阻碍了许多潜在的化合物获得批准。一个有重大改进机会的领域是筛选新化合物的初步疗效的过程，也称为早期第二阶段试验。早期的第二阶段试验结合了人体实验室的范例来评估相关的临床结构，如渴求和对酒精的主观反应。然而，这些对照范例往往缺乏临床试验的生态有效性。因此，如果将实验室检测的内部有效性和临床试验的外部有效性结合起来，早期的2期试验可能会更有效，也更有临床意义。为此，本研究旨在根据戒烟文献，开发和验证一种新的早期疗效范例，以筛选治疗AUD的新药物。作为一种成熟的AUD药物，纳曲酮将作为一种积极的对照来测试实践戒断尝试模式和一种有前景的AUD药物疗法varenicline的疗效。目前有AUD报告内在动机改变饮酒的人将在研究药物治疗期间完成为期一周的“戒烟尝试”。参与者被随机分为纳曲酮、伐伦克林或安慰剂。在戒酒练习期间，参与者将通过电话完成日常访问，并填写关于他们饮酒、饮酒渴望和情绪的在线问卷。此外，参与者将接受两次酒精提示反应会议。这项研究的成功完成将通过提出和验证一种用于筛选AUD药物疗法的新的早期疗效模型来推动药物开发，该模型反过来可以作为一种有效的策略，来决定是否继续进行临床试验。临床试验.gov NCT04249882。注册日期为2020年1月31日。
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.
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影响因子：
5
作者：
COHEN, S;KAMARCK, T;MERMELSTEIN, R
通讯作者：
MERMELSTEIN, R
影响因子：
3.2
作者：
Del Re, A. C.;Maisel, Natalya;Finney, John
通讯作者：
Finney, John
DOI：
10.1001/jama.2018.11406
发表时间：
2018-08-28
期刊：
JAMA
影响因子：
--
作者：
Kranzler HR;Soyka M
通讯作者：
Soyka M
影响因子：
3.8
作者：
Adamson, SJ;Sellman, JD
通讯作者：
Sellman, JD
影响因子：
5
作者：
Blomqvist, O;Ericson, M;Soderpalm, B
通讯作者：
Soderpalm, B