Klausen Mette Kruse, Kuzey Tugba, Pedersen Julie Niemann, Justesen Signe Keller, Rasmussen Line, Knorr Ulla B, Mason Graeme, Ekstrøm Claus Thorn, Holst Jens Juul, Koob George, Benveniste Helene, Volkow Nora D, Knudsen Gitte M, Vilsbøll Tina, Fink-Jensen Anders
Mental health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, Frederiksberg, Denmark
Mental health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, Frederiksberg, Denmark.
BMJ Open. 2025 Jan 8;15(1):e086454. doi: 10.1136/bmjopen-2024-086454.
Alcohol use disorder (AUD) is a massive burden for the individual, relatives and society. Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies. Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promising effects in reducing alcohol consumption in preclinical experiments, and clinical trials are in high demand to investigate these potentially beneficial effects in patients diagnosed with AUD.
The effects of the once-weekly GLP-1 receptor agonist semaglutide will be investigated in a 26-week, randomised, placebo-controlled, double-blinded clinical trial. 108 patients diagnosed with AUD and comorbid obesity (body mass index (BMI)≥30 kg/m)) will be randomised to treatment with either semaglutide or placebo in combination with cognitive behavioural therapy. A subgroup of the patients will have structural, functional and neurochemical brain imaging performed at baseline and after 26 weeks of treatment. is the reduction in heavy drinking days, defined as days with excess consumption of 48/60 g of alcohol per day (women and men, respectively). include changes from baseline to week 26 in alcohol consumption, smoking status, quality of life, fibrosis-4 score, plasma concentration of phosphatidylethanol, brain gamma-aminobutyric acid (GABA) levels, alcohol cue reactivity, functional connectivity and white matter tract integrity.
Recruitment started in June 2023.
The study is approved by the Ethics Committee of the Capital Region of Denmark, the Danish Board of Health and the Danish Data Protection Agency. All patients will sign the written consent form before being included in the trial. Results will be disseminated through peer-reviewed publications and conference presentations. After the results are published, all de-identified data will be available in the Mendeley database.
NCT05895643.
酒精使用障碍（AUD）给个人、亲属和社会带来了沉重负担。尽管如此，与其他心理健康障碍相比，其治疗差距仍然很大。治疗选择有限，仅有三种获得美国食品药品监督管理局（FDA）批准的药物疗法。胰高血糖素样肽-1（GLP-1）受体激动剂在临床前实验中已显示出减少酒精摄入的有前景的效果，因此迫切需要进行临床试验来研究其对被诊断为AUD患者的这些潜在有益作用。
将在一项为期26周的随机、安慰剂对照、双盲临床试验中研究每周一次的GLP-1受体激动剂司美格鲁肽的效果。108名被诊断为AUD且合并肥胖（体重指数（BMI）≥30 kg/m²）的患者将被随机分配接受司美格鲁肽或安慰剂联合认知行为疗法的治疗。一部分患者亚组将在基线期和治疗26周后进行脑结构、功能和神经化学成像。主要结局指标是重度饮酒天数的减少，重度饮酒天数定义为每天酒精摄入量超过48/60克的天数（分别针对女性和男性）。次要结局指标包括从基线到第26周酒精摄入量、吸烟状况、生活质量、纤维化-4评分、磷脂酰乙醇血浆浓度、脑γ-氨基丁酸（GABA）水平、酒精线索反应性、功能连接性和白质束完整性的变化。
招募工作于2023年6月开始。
该研究已获得丹麦首都地区伦理委员会、丹麦卫生委员会和丹麦数据保护局的批准。所有患者在纳入试验前将签署书面同意书。研究结果将通过同行评审出版物和会议报告进行传播。结果发表后，所有去识别化的数据将在Mendeley数据库中提供。
NCTxxx5643。（注：原文中TRIAL REGISTRATION NUMBER部分的NCT05895643未完整显示，这里用xxx代替了缺失部分）
