NCT05895643已完成2 期
Does the Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?
Psychiatric Centre Rigshospitalet1 个研究点 分布在 1 个国家目标入组 108 人开始时间: 2023年6月13日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Change in heavy drinking days
研究概览
简要总结
This 26-week long, double-blinded randomized clinical trial aims to investigate the effects of the GLP-1 receptor agonist semaglutide s.c. vs placebo on alcohol consumption in 108 patients diagnosed with alcohol use disorder and comorbid obesity (BMI>30 kg/m2).
Patients will be treated for 26 weeks with semaglutide subcutaneously (s.c.) once weekly or placebo. The medication will be provided as a supplement to standardised cognitive behavioural therapy. A subgroup of the patients will have two brain scans (Magnetic Resonance Spectroscopy (MRS) and functional Magnetic Resonance Imaging (fMRI)) conducted in one scan session at week 0 and 26.
The primary endpoint is the percentage-point reduction in total number of heavy drinking days, defined as days with an excess intake of 48/60 grams of alcohol per day (women and men, respectively) from baseline to follow-up after 26 weeks of treatment, measured by the timeline followback (TLFB) method.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed oral and written consent
- •Diagnosed with alcohol dependence according to the criteria of the International Classification of Diseases 10 (ICD-10), and diagnosed with alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
- •Alcohol use disorder identification test (AUDIT) score >15
- •Body mass index (BMI) above or equal to 30 kg/m2
- •Age 18 - 70 years (both included)
- •Heavy alcohol drinking defined as more than 6 days with alcohol consumption over 4 units (48 g alcohol) for women and 5 units (60 g alcohol) for men during a consecutive 30-day period, within 40 days prior to baseline evaluation, measured by the TLFB method. The 30-day period will be the 30 consecutive days with the biggest alcohol intake (most heavy drinking days and the largest amount of total alcohol) out of the 40 days.
排除标准
- •Severe psychiatric disease, defined as a diagnosis of schizophrenia, paranoid psychosis, bipolar disorder or mental retardation
- •A history of delirium tremens or alcohol withdrawal seizures
- •No serious withdrawal symptoms at inclusion (a score higher than 9 on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)) at baseline examinations
- •Present or former neurological disease, including traumatic brain injury
- •Type 1 diabetes, type 2 diabetes in poor glycaemic control (defined as HbA1c ≥48 mmol/l or fasting plasma glucose above 7.0 mmol/l at inclusion)
- •Females of childbearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant within the next 9 months (26 weeks plus two months after discontinuation of semaglutide), or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device, bilateral tubal occlusion, vasectomised partner, sexual abstinence).
- •Pregnancy (serum human chorionic gonadotropin (hCG) > 3 U/L at inclusion)
- •Impaired hepatic function (liver transaminases >3 times the upper limit)
- •Impaired renal function (eGFR < 50 ml/min and/or plasma creatinine >150 μmol/l)
- •Impaired pancreatic function (any history of acute or chronic pancreatitis and/or amylase > 2 times upper limit)
- •Former medullary thyroid carcinoma (MTC) and/or family history with MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- •Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
- •Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg)
- •Concomitant pharmacotherapy against alcohol use disorder, i.e., disulfiram, naltrexone, acamprosate, or nalmefene, since the first of the 30 drinking days registered for inclusion at the TLFB-schedule.
- •Receiving any investigational drug within the last three months
- •Use of weight-lowering pharmacotherapy within the preceding 3 months
- •Any other active substance use defined as a DUDIT-score >1 (except nicotine)
- •Hypersensitivity to the active substance or any of the excipients
- •Only for patients undergoing brain scans:
- •o Contraindications for undergoing an MRI scan (magnetic implants, pacemaker, claustrophobia, etc.)
- •Unable to speak and/or understand Danish
- •Any condition that the investigator feels would interfere with trial participation
研究组 & 干预措施
semaglutide
Experimental
Wegovy once-weekly s.c.titrated to a maximum dose of 2.4 mg
干预措施: Semaglutide Injectable Product (Drug)
placebo
Placebo Comparator
Saline s.c. once-weekly
干预措施: Placebo (Drug)
结局指标
主要结局
Change in heavy drinking days
时间窗: From baseline to 26 weeks of treatment
Change in alcohol consumption, defined as the change in percentage of heavy drinking days during a period of 30 consecutive days, after 26 weeks of treatment adjusted for baseline (percentage points (pp)). A heavy drinking day is defined as more than 60/48 grams (men/women) of alcohol in one day, measured with the validated timeline follow-back (TLFB) method.
次要结局
- Change in heavy drinking days adjusted for maximum tolerable semaglutide dose given(From baseline to 26 weeks of treatment)
- Change in heavy drinking days adjusted for weightloss(From baseline to 26 weeks of treatment)
- Total alcohol consumption(From baseline to 26 weeks of treatment)
- Drinks per day(From baseline to 26 weeks of treatment)
- Days without alcohol consumption(From baseline to 26 weeks of treatment)
- Time to relapse(From baseline to 26 weeks of treatment)
- Time to relapse (heavy drinking day)(From baseline to 26 weeks of treatment)
- World Health Organization (WHO) Risk Levels of Alcohol Consumption(From baseline to 26 weeks of treatment)
- Penn Alcohol Craving Scale (PACS) score(From baseline to 26 weeks of treatment)
- Alcohol Use Disorder Identification Test (AUDIT) score(From baseline to 26 weeks of treatment)
- Drug Use Disorders Identification Test (DUDIT) score(From baseline to 26 weeks of treatment)
- Fibrosis-4 (FIB4) score(From baseline to 26 weeks of treatment)
- Measure of life quality - World Health Organization Quality of Life brief (WHOQOL-BREF) score(From baseline to 26 weeks of treatment)
- Fagerströms Test for Nicotine Dependence score(From baseline to 26 weeks of treatment)
- Gamma-glutamyl transferase (GGT)(From baseline to 26 weeks of treatment)
- Alanine transaminase (ALAT)(From baseline to 26 weeks of treatment)
- Phosphatidyl ethanol (PEth)(From baseline to 26 weeks of treatment)
- Mean cell volume (MCV)(From baseline to 26 weeks of treatment)
- Body weight(From baseline to 26 weeks of treatment)
- Blood pressure(From baseline to 26 weeks of treatment)
- Pulse(From baseline to 26 weeks of treatment)
- Waist circumference(From baseline to 26 weeks of treatment)
- Glycaemic control parameters(From baseline to 26 weeks of treatment)
- MRS brain gamma-aminobutyric acid (GABA) levels(From baseline to 26 weeks of treatment)
- fMRI alcohol cue-reactivity(From baseline to 26 weeks of treatment)
研究者
Anders Fink-Jensen, MD, DMSci
Professor
Mental Health Services in the Capital Region, Denmark
研究点 (1)
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