异丁司特用于酒精使用障碍：一项II期随机临床试验的研究方案
Ibudilast for alcohol use disorder: study protocol for a phase II randomized clinical trial.
作者信息
Burnette Elizabeth M, Baskerville Wave-Ananda, Grodin Erica N, Ray Lara A
机构信息
Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Interdepartmental Program for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA.
出版信息
Trials. 2020 Sep 11;21(1):779. doi: 10.1186/s13063-020-04670-y.
BACKGROUND
Alcohol use disorder (AUD) is a chronic and relapsing condition for which current pharmacological treatments are only modestly effective. The development of efficacious medications for AUD remains a high research priority with recent emphasis on identifying novel molecular targets for AUD treatment and to efficiently screen new compounds aimed at those targets. Ibudilast, a phosphodiesterase inhibitor, has been advanced as a novel addiction pharmacotherapy that targets neurotrophin signaling and neuroimmune function.
METHODS
This study will conduct a 12-week, double-blind, placebo controlled randomized clinical trial of ibudilast (50 mg BID) for AUD treatment. We will randomize 132 treatment-seeking men and women with current AUD. We will collect a number of alcohol consumption outcomes. Primary among these is percent heavy drinking days (PHDD); secondary drinking outcomes include drinks per day, drinks per drinking day, percent days abstinent, percent subjects with no heavy drinking days, and percent subjects abstinent, as well as measures of alcohol craving and negative mood. Additionally, participants will have the option to opt-in to a neuroimaging session in which we examine the effects of ibudilast on neural activation to psychosocial stress and alcohol cues. Finally, we will also collect plasma levels of proinflammatory markers, as well as subjective and biological (salivary cortisol) markers of stress response.
DISCUSSION
This study will further develop ibudilast, a safe and promising novel compound with strong preclinical and clinical safety data for AUD, and will probe biological mechanisms underlying the effects of Ibudilast on stress, neuroinflammation, and alcohol cue-reactivity and craving. If ibudilast proves superior to placebo in this study, it will set the stage for a confirmatory multi-site trial leading to FDA approval of a novel AUD treatment.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03594435 "Ibudilast for the Treatment of Alcohol Use Disorder". Registered on 20 July 2018.
背景
酒精使用障碍（AUD）是一种慢性复发性疾病，目前的药物治疗效果仅一般。开发有效的AUD药物仍然是一个高度优先的研究领域，最近重点在于确定AUD治疗的新分子靶点，并有效筛选针对这些靶点的新化合物。异丁司特是一种磷酸二酯酶抑制剂，已被提出作为一种针对神经营养因子信号传导和神经免疫功能的新型成瘾药物疗法。
方法
本研究将进行一项为期12周的双盲、安慰剂对照的随机临床试验，使用异丁司特（50毫克，每日两次）治疗AUD。我们将把132名有AUD且寻求治疗的男性和女性随机分组。我们将收集多项饮酒结果。其中主要的是重度饮酒天数百分比（PHDD）；次要饮酒结果包括每日饮酒量、每次饮酒日饮酒量、戒酒天数百分比、无重度饮酒天数的受试者百分比、戒酒受试者百分比，以及酒精渴望和负面情绪的测量指标。此外，参与者将有机会选择参加一次神经影像学检查，在此检查中我们将研究异丁司特对心理社会应激和酒精线索的神经激活的影响。最后，我们还将收集促炎标志物的血浆水平，以及应激反应的主观和生物学（唾液皮质醇）标志物。
讨论
本研究将进一步开发异丁司特，这是一种安全且有前景的新型化合物，具有针对AUD的强大临床前和临床安全性数据，并将探究异丁司特对应激、神经炎症、酒精线索反应性和渴望的影响背后的生物学机制。如果异丁司特在本研究中证明优于安慰剂，它将为一项确证性多中心试验奠定基础，从而使一种新型AUD治疗获得美国食品药品监督管理局（FDA）批准。
试验注册
ClinicalTrials.gov NCT03594435“异丁司特治疗酒精使用障碍”。于2018年7月20日注册。
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