Clinical trial NCT05895643: Does Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?
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?
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alcohol Abuse
Alcohol Addiction
Alcohol Dependence
Alcohol Use Disorder
Keywords: GLP-1
Glucagon-like peptide 1
semaglutide
fMRI
MRS
Lead sponsor: Psychiatric Centre Rigshospitalet
Sponsor class: OTHER
Collaborators: name: Neurobiology Research Unit
First posted: 2023-06-08
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change in heavy drinking days
timeFrame: From baseline to 26 weeks of treatment
Secondary outcomes:
measure: Change in heavy drinking days adjusted for maximum tolerable semaglutide dose given
timeFrame: From baseline to 26 weeks of treatment
measure: Change in heavy drinking days adjusted for weightloss
timeFrame: From baseline to 26 weeks of treatment
measure: Total alcohol consumption
timeFrame: From baseline to 26 weeks of treatment
measure: Drinks per day
timeFrame: From baseline to 26 weeks of treatment
measure: Days without alcohol consumption
timeFrame: From baseline to 26 weeks of treatment
measure: Time to relapse
timeFrame: From baseline to 26 weeks of treatment
measure: Time to relapse (heavy drinking day)
timeFrame: From baseline to 26 weeks of treatment
measure: World Health Organization (WHO) Risk Levels of Alcohol Consumption
timeFrame: From baseline to 26 weeks of treatment
measure: Penn Alcohol Craving Scale (PACS) score
timeFrame: From baseline to 26 weeks of treatment
measure: Alcohol Use Disorder Identification Test (AUDIT) score
timeFrame: From baseline to 26 weeks of treatment
measure: Drug Use Disorders Identification Test (DUDIT) score
timeFrame: From baseline to 26 weeks of treatment
measure: Fibrosis-4 (FIB4) score
timeFrame: From baseline to 26 weeks of treatment
measure: Measure of life quality - World Health Organization Quality of Life brief (WHOQOL-BREF) score
timeFrame: From baseline to 26 weeks of treatment
measure: Fagerströms Test for Nicotine Dependence score
timeFrame: From baseline to 26 weeks of treatment
measure: Gamma-glutamyl transferase (GGT)
timeFrame: From baseline to 26 weeks of treatment
measure: Alanine transaminase (ALAT)
timeFrame: From baseline to 26 weeks of treatment
measure: Phosphatidyl ethanol (PEth)
timeFrame: From baseline to 26 weeks of treatment
measure: Mean cell volume (MCV)
timeFrame: From baseline to 26 weeks of treatment
measure: Body weight
timeFrame: From baseline to 26 weeks of treatment
measure: Blood pressure
timeFrame: From baseline to 26 weeks of treatment
measure: Pulse
timeFrame: From baseline to 26 weeks of treatment
measure: Waist circumference
timeFrame: From baseline to 26 weeks of treatment
measure: Glycaemic control parameters
timeFrame: From baseline to 26 weeks of treatment
measure: MRS brain gamma-aminobutyric acid (GABA) levels
timeFrame: From baseline to 26 weeks of treatment
measure: fMRI alcohol cue-reactivity
timeFrame: From baseline to 26 weeks of treatment
Other outcomes:
Locations:
city: Frederiksberg
country: Denmark
facility: Psychiatric Center Copenhagen, Frederiksberg Hospital
Study officials:
affiliation: Mental Health Services in the Capital Region, Denmark
name: Anders Fink-Jensen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: