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

June 13, 2023 updated by: Anders Fink-Jensen, MD, DMSci, Psychiatric Centre Rigshospitalet

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in heavy drinking days
Time Frame: 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.
From baseline to 26 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in heavy drinking days adjusted for maximum tolerable semaglutide dose given
Time Frame: 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.
From baseline to 26 weeks of treatment
Change in heavy drinking days adjusted for weightloss
Time Frame: 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
From baseline to 26 weeks of treatment
Total alcohol consumption
Time Frame: From baseline to 26 weeks of treatment
Change in total alcohol consumption /gram/last 30 consecutive days)
From baseline to 26 weeks of treatment
Days without alcohol consumption
Time Frame: From baseline to 26 weeks of treatment
Number of days without alcohol consumption in the last 30 consecutive days
From baseline to 26 weeks of treatment
Time to relapse
Time Frame: From baseline to 26 weeks of treatment
Time to relapse, defined as the time to first alcohol intake
From baseline to 26 weeks of treatment
Time to relapse (heavy drinking day)
Time Frame: From baseline to 26 weeks of treatment
Time to first heavy drinking day
From baseline to 26 weeks of treatment
World Health Organization (WHO) Risk Levels of Alcohol Consumption
Time Frame: 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.
From baseline to 26 weeks of treatment
Penn Alcohol Craving Scale (PACS) score
Time Frame: 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.
From baseline to 26 weeks of treatment
Alcohol Use Disorder Identification Test (AUDIT) score
Time Frame: 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.
From baseline to 26 weeks of treatment
Drug Use Disorders Identification Test (DUDIT) score
Time Frame: 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.
From baseline to 26 weeks of treatment
Fibrosis-4 (FIB4) score
Time Frame: 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.
From baseline to 26 weeks of treatment
Measure of life quality - World Health Organization Quality of Life brief (WHOQOL-BREF) score
Time Frame: 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.
From baseline to 26 weeks of treatment
Fagerströms Test for Nicotine Dependence score
Time Frame: 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.
From baseline to 26 weeks of treatment
Gamma-glutamyl transferase (GGT)
Time Frame: From baseline to 26 weeks of treatment
Change in blood gamma-glutamyl transferase (GGT)
From baseline to 26 weeks of treatment
Alanine transaminase (ALAT)
Time Frame: From baseline to 26 weeks of treatment
Change in blood alanine transaminase (ALAT)
From baseline to 26 weeks of treatment
Phosphatidyl ethanol (PEth)
Time Frame: From baseline to 26 weeks of treatment
Change in plasma levels of phosphatidyl ethanol (PEth)
From baseline to 26 weeks of treatment
Mean cell volume (MCV)
Time Frame: From baseline to 26 weeks of treatment
Change in blood mean cell volume (MCV)
From baseline to 26 weeks of treatment
Body weight
Time Frame: From baseline to 26 weeks of treatment
Change in Body weight
From baseline to 26 weeks of treatment
Blood pressure
Time Frame: From baseline to 26 weeks of treatment
Change in blood pressure (both systolic and diastolic)
From baseline to 26 weeks of treatment
Pulse
Time Frame: From baseline to 26 weeks of treatment
Change in pulse
From baseline to 26 weeks of treatment
Waist circumference
Time Frame: From baseline to 26 weeks of treatment
Change in waist circumference
From baseline to 26 weeks of treatment
Glycaemic control parameters
Time Frame: From baseline to 26 weeks of treatment
Change in HbA1c
From baseline to 26 weeks of treatment
MRS brain gamma-aminobutyric acid (GABA) levels
Time Frame: From baseline to 26 weeks of treatment
Change in brain GABA levels (cortical, caudate, and putamen) assessed by MRS brain scans
From baseline to 26 weeks of treatment
fMRI alcohol cue-reactivity
Time Frame: 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
From baseline to 26 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Psychiatric Centre Rigshospitalet

Collaborators

Neurobiology Research Unit

Investigators

  • Principal Investigator: Anders Fink-Jensen, MD, DMSc, Mental Health Centre Copenhagen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2023

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

May 26, 2023

First Submitted That Met QC Criteria

June 6, 2023

First Posted (Actual)

June 8, 2023

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 13, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • The SEMALCO study
  • U1111-1286-6919 (Registry Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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