Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial)

Abstract

Introduction: Alcohol use disorder (AUD) is a massive burden for the individual, relatives and society. Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies. Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promising effects in reducing alcohol consumption in preclinical experiments, and clinical trials are in high demand to investigate these potentially beneficial effects in patients diagnosed with AUD.

Methods and analysis: The effects of the once-weekly GLP-1 receptor agonist semaglutide will be investigated in a 26-week, randomised, placebo-controlled, double-blinded clinical trial. 108 patients diagnosed with AUD and comorbid obesity (body mass index (BMI)≥30 kg/m²)) will be randomised to treatment with either semaglutide or placebo in combination with cognitive behavioural therapy. A subgroup of the patients will have structural, functional and neurochemical brain imaging performed at baseline and after 26 weeks of treatment. The primary endpoint is the reduction in heavy drinking days, defined as days with excess consumption of 48/60 g of alcohol per day (women and men, respectively). Secondary endpoints include changes from baseline to week 26 in alcohol consumption, smoking status, quality of life, fibrosis-4 score, plasma concentration of phosphatidylethanol, brain gamma-aminobutyric acid (GABA) levels, alcohol cue reactivity, functional connectivity and white matter tract integrity.

Status: Recruitment started in June 2023.

Ethics and dissemination: The study is approved by the Ethics Committee of the Capital Region of Denmark, the Danish Board of Health and the Danish Data Protection Agency. All patients will sign the written consent form before being included in the trial. Results will be disseminated through peer-reviewed publications and conference presentations. After the results are published, all de-identified data will be available in the Mendeley database.

Trial registration number: NCT05895643.

Keywords: Clinical Trial; Ethanol; Functional Magnetic Resonance Imaging; Patients; Randomised Controlled Trial; Substance misuse.

Figure 1. AE, adverse events; AR, adverse reactions; DTI, diffusion tensor imaging; fMRI, functional MRI; MRS, magnetic resonance spectroscopy; SAE, serious adverse events; SAR, serious adverse reactions; sc., subcutaneous; TLFB, timeline follow back

Figure 2. The first injection of the assigned treatment is given at week 0. Cognitive behavioural therapy is provided in 10 sessions during the 26 weeks of inclusion. AUDIT, alcohol use disorders identification test; CIWA-AR, Clinical Institute Withdrawal Assessment for Alcohol-revised; DUDIT, Drug Use Disorders Identification Test; fMRI, functional MRI; MDI, major depressive inventory; PACS, Penn Alcohol Craving Scale; TLFB, timeline followback; WHOQOL-BREF, WHO Quality of Life Bref.