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

• ClinicalTrials.gov Identifier: NCT05895643
• Recruitment Status: Recruiting
• First Posted: June 8, 2023
• Last Update Posted: June 15, 2023
• Sponsor: Psychiatric Centre Rigshospitalet
• Collaborator: Neurobiology Research Unit
• Information provided by (Responsible Party): Anders Fink-Jensen, MD, DMSci, Mental Health Services in the Capital Region, Denmark

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 (Clinical Trial)
• Estimated 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: June 13, 2023
• Estimated Primary Completion Date: September 2026
• Estimated Study Completion Date: March 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 Name: Wegovy
Placebo Comparator: placebo; Saline s.c. once-weekly	Drug: Placebo; Once weekly injections s.c with placebo (BD Posiflush); Other Name: BD Posiflush (saline)

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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
3. Total alcohol consumption [ Time Frame: From baseline to 26 weeks of treatment ]
   Change in total alcohol consumption /gram/last 30 consecutive days)
4. 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
5. Time to relapse [ Time Frame: From baseline to 26 weeks of treatment ]
   Time to relapse, defined as the time to first alcohol intake
6. Time to relapse (heavy drinking day) [ Time Frame: From baseline to 26 weeks of treatment ]
   Time to first heavy drinking day
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. Gamma-glutamyl transferase (GGT) [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in blood gamma-glutamyl transferase (GGT)
15. Alanine transaminase (ALAT) [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in blood alanine transaminase (ALAT)
16. Phosphatidyl ethanol (PEth) [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in plasma levels of phosphatidyl ethanol (PEth)
17. Mean cell volume (MCV) [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in blood mean cell volume (MCV)
18. Body weight [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in Body weight
19. Blood pressure [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in blood pressure (both systolic and diastolic)
20. Pulse [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in pulse
21. Waist circumference [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in waist circumference
22. Glycaemic control parameters [ Time Frame: From baseline to 26 weeks of treatment ]
    Change in HbA1c
23. 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
24. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Mette Klausen, MD, phd; +4522649599; mette.kruse.klausen@regionh.dk

Contact: Anders Fink-Jensen, MD, DMSc; +4522755843; anders.fink-jensen@regionh.dk

Locations

Denmark

Psychiatric Center Copenhagen, Frederiksberg Hospital; Recruiting

Frederiksberg, Denmark, 2000

Contact: Mette Klausen, MD, PhD +45 24835004 mette.kruse.klausen@regionh.dk

Contact: Anders C Fink-Jensen +45 38647072 anders.fink-jensen@regionh.dk

Sponsors and Collaborators

Psychiatric Centre Rigshospitalet

Neurobiology Research Unit

Investigators

• Principal Investigator: Anders Fink-Jensen, MD, DMSc; Mental Health Services in the Capital Region, Denmark

  Study Documents (Full-Text)

Documents provided by Anders Fink-Jensen, MD, DMSci, Mental Health Services in the Capital Region, Denmark:

Study Protocol  [PDF] April 24, 2023

More Information

• Responsible Party: Anders Fink-Jensen, MD, DMSci, Professor, Mental Health Services in the Capital Region, Denmark
• ClinicalTrials.gov Identifier: NCT05895643
• Other Study ID Numbers: The SEMALCO study; U1111-1286-6919 ( Registry Identifier: Universal Trial Number )
• First Posted: June 8, 2023
• Last Update Posted: June 15, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anders Fink-Jensen, MD, DMSci, Mental Health Services in the Capital Region, Denmark:

GLP-1; Glucagon-like peptide 1; semaglutide; fMRI; MRS

Additional relevant MeSH terms:

Alcoholism; Alcohol Drinking; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Semaglutide; Glucagon-Like Peptide-1 Receptor Agonists; Hypoglycemic Agents; Physiological Effects of Drugs