Does Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?

Phase 2

Active, not recruiting

• Conditions: Alcohol Dependence; Alcohol Use Disorder; Alcohol Addiction; Alcohol Abuse
• Interventions: Drug: Semaglutide Injectable Product; Drug: Placebo

• Registration Number: NCT05895643
• Lead Sponsor: Psychiatric Centre Rigshospitalet

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-26
• Study First Submitted QC: 2023-06-06
• Study First Posted: 2023-06-08
• Study Start: 2023-06-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-17
• Primary Completion: 2025-08
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
semaglutide	Semaglutide Injectable Product	Wegovy once-weekly s.c.titrated to a maximum dose of 2.4 mg
placebo	Placebo	Saline s.c. once-weekly

Primary Outcome Measures

Name	Time	Method
Change in heavy drinking days	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.

Secondary Outcome Measures

Name	Time	Method
Change in heavy drinking days adjusted for maximum tolerable semaglutide dose given	From baseline to 26 weeks of treatment	Change in heavy drinking days during a period of 30 consecutive days, after 26 weeks of treatment adjusted for baseline (percentage points (pp)) and maximum tolerable semaglutide dose given.
Change in heavy drinking days adjusted for weightloss	From baseline to 26 weeks of treatment	Change in heavy drinking days during a period of 30 consecutive days, after 26 weeks of treatment adjusted for baseline (percentage points (pp)) and weight loss during the 26 weeks of treatment
Total alcohol consumption	From baseline to 26 weeks of treatment	Change in total alcohol consumption /gram/last 30 consecutive days)
Drinks per day	From baseline to 26 weeks of treatment	Change in total drinks per day (last 30 consecutive days)
Days without alcohol consumption	From baseline to 26 weeks of treatment	Number of days without alcohol consumption in the last 30 consecutive days
Time to relapse	From baseline to 26 weeks of treatment	Time to relapse, defined as the time to first alcohol intake
Time to relapse (heavy drinking day)	From baseline to 26 weeks of treatment	Time to first heavy drinking day
World Health Organization (WHO) Risk Levels of Alcohol Consumption	From baseline to 26 weeks of treatment	Change in WHO alcohol risk level in the last 30 consecutive days, measured with the validated timeline follow-back (TLFB) method.
Penn Alcohol Craving Scale (PACS) score	From baseline to 26 weeks of treatment	Change in Penn Alcohol Craving Scale (PACS) score. Minimum score = 0, maximum score =30. A high score means a worse outcome.
Alcohol Use Disorder Identification Test (AUDIT) score	From baseline to 26 weeks of treatment	Change in Alcohol Use Disorder Identification Test (AUDIT) score. Minimum score = 0, maximum score =40. A high score means a worse outcome.
Drug Use Disorders Identification Test (DUDIT) score	From baseline to 26 weeks of treatment	Change in Drug Use Disorders Identification Test (DUDIT) score. Minimum score = 0, maximum score =44. A high score means a worse outcome.
Fibrosis-4 (FIB4) score	From baseline to 26 weeks of treatment	Change in Fibrosis-4 (FIB4) score, calculated from the parameters: the patient's age, blood aspartate aminotransferase levels (ASAT), thrombocytes and alanine transaminase (ALAT). A higher score means a worse outcome.
Measure of life quality - World Health Organization Quality of Life brief (WHOQOL-BREF) score	From baseline to 26 weeks of treatment	Change in Measures of Health (WHOQOL-BREF) score. Minimum score = 26, maximum score =130. Higher scores mean a better outcome in items 1-2 + 10-25. A higher score in items 3-9 + 26 means a worse outcome.
Fagerströms Test for Nicotine Dependence score	From baseline to 26 weeks of treatment	Change in Fagerströms Test for Nicotine Dependence score. Minimum score = 0, maximum score =10. A high score means a worse outcome.
Gamma-glutamyl transferase (GGT)	From baseline to 26 weeks of treatment	Change in blood gamma-glutamyl transferase (GGT)
Alanine transaminase (ALAT)	From baseline to 26 weeks of treatment	Change in blood alanine transaminase (ALAT)
Phosphatidyl ethanol (PEth)	From baseline to 26 weeks of treatment	Change in plasma levels of phosphatidyl ethanol (PEth)
Mean cell volume (MCV)	From baseline to 26 weeks of treatment	Change in blood mean cell volume (MCV)
Body weight	From baseline to 26 weeks of treatment	Change in Body weight
Blood pressure	From baseline to 26 weeks of treatment	Change in blood pressure (both systolic and diastolic)
Pulse	From baseline to 26 weeks of treatment	Change in pulse
Waist circumference	From baseline to 26 weeks of treatment	Change in waist circumference
Glycaemic control parameters	From baseline to 26 weeks of treatment	Change in HbA1c
MRS brain gamma-aminobutyric acid (GABA) levels	From baseline to 26 weeks of treatment	Change in brain GABA levels (cortical, caudate, and putamen) assessed by MRS brain scans
fMRI alcohol cue-reactivity	From baseline to 26 weeks of treatment	Change in brain alcohol cue-response in reward-processing brain regions (ventral and dorsal striatum, puta-men, nucleus accumbens, and caudate), including the septal area assessed by fMRI brain scans

Trial Locations

Locations (1)

Psychiatric Center Copenhagen, Frederiksberg Hospital; 🇩🇰 Frederiksberg, Denmark