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

Sponsor

Psychiatric Centre Rigshospitalet (Other)

Overall Status

Recruiting

CT.gov ID

NCT05895643

Collaborator

Neurobiology Research Unit (Other)

108

Enrollment

Location

Arms

44.6

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Abuse Alcohol Addiction Alcohol Dependence Alcohol Use Disorder	Drug: Semaglutide Injectable Product Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Does the Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?

Actual Study Start Date :

Jun 13, 2023

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: semaglutide Wegovy once-weekly s.c.titrated to a maximum dose of 2.4 mg	Drug: Semaglutide Injectable Product Once weekly injections s.c with semaglutide (Wegovy) Other Names: Wegovy
Placebo Comparator: placebo Saline s.c. once-weekly	Drug: Placebo Once weekly injections s.c with placebo (BD Posiflush) Other Names: BD Posiflush (saline)

Arm

Intervention/Treatment

Experimental: semaglutide

Wegovy once-weekly s.c.titrated to a maximum dose of 2.4 mg

Drug: Semaglutide Injectable Product

Once weekly injections s.c with semaglutide (Wegovy)

Other Names:

Wegovy

Placebo Comparator: placebo

Saline s.c. once-weekly

Drug: Placebo

Once weekly injections s.c with placebo (BD Posiflush)

Other Names:

BD Posiflush (saline)

Outcome Measures

Primary Outcome Measures

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

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)
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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: