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

Alcohol Use Disorder Clinical Trial

— SEMALCO  

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?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05895643
• Other study ID #: The SEMALCO study
• Secondary ID: U1111-1286-6919
• Status: Recruiting
• Phase: Phase 2
• Start date: June 13, 2023
• Est. completion date: March 2027

Study information

• Verified date: June 2023
• Source: Psychiatric Centre Rigshospitalet
• Contact: Mette Klausen, MD, phd
• Phone: +4522649599
• Email: mette.kruse.klausen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: March 2027
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Abuse
• Alcohol Addiction
• Alcohol Dependence
• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

Drug:
• Semaglutide Injectable Product
Once weekly injections s.c with semaglutide (Wegovy)
• Placebo
Once weekly injections s.c with placebo (BD Posiflush)

Locations

Country	Name	City	State
Denmark	Psychiatric Center Copenhagen, Frederiksberg Hospital	Frederiksberg

Sponsors (2)

Lead Sponsor	Collaborator
Psychiatric Centre Rigshospitalet	Neurobiology Research Unit

Country where clinical trial is conducted

Denmark, 

Outcome

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