NCT07249554

Combination Therapy for Alcohol Use Disorder

Preliminary Safety and Efficacy of Semaglutide and Naltrexone Combination Therapy for Alcohol Use Disorder

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This human laboratory study will collect preliminary safety and efficacy data from a sample of participants enrolled in a 4-week in-patient treatment program for alcohol use disorder.

Detailed description

Approximately 29 million persons in the United States aged 12 and older experienced a form of Alcohol Use Disorder (AUD) in 2023. Currently, only three pharmacotherapies are FDA-approved to treat AUD: acamprosate, naltrexone, and disulfiram. As monotherapies, these have shown moderate efficacy in reducing alcohol consumption and increasing abstinence. There is some evidence that therapeutic effects can be enhanced when combined with other medications. Recently, emerging preclinical evidence suggests that endogenous GLP-1 signaling plays a role in alcohol-mediated behaviors. Further, growing clinical data suggest that GLP-1 agonists (e.g., Wegovy, Rybelsus, Mounjaro) may be effective for the treatment of AUD. Studies evaluating the efficacy of GLP-1 agonists in combination with FDA-approved medications for AUD have yet to be conducted. The investigators hypothesize that combining a GLP-1 agonist and naltrexone may be more effective for reducing dimensions of AUD than naltrexone alone. The goal of this study is to collect preliminary safety and efficacy data from a sample of participants enrolled in a 4-week in-patient treatment program for AUD. Following one week of in-patient enrollment, participants will be randomized to one of three conditions in a double dummy design: placebo + placebo, GLP-1 + placebo, or GLP-1 + naltrexone. All study medications will be administered orally. Participants randomized to active GLP-1 conditions will receive 3 mg during study week 1 and can increase to 7 mg during week 2. Participants will attend study visits in a 14-day period to complete assessments of alcohol craving, alcohol demand, anhedonia, eating behaviors, and subjective effects. Participants will also provide vitals and biosamples to evaluate health outcomes.

Conditions

• Alcohol Use Disorder

Interventions

Type	Name	Description
DRUG	Placebo	Over-encapsulated non-active microcrystalline cellulose
DRUG	Glucagon-Like Peptide-1 Agonist (GLP-1)	Over-encapsulated Glucagon-Like Peptide-1 Agonist (GLP-1) oral tablets
DRUG	Naltrexone (oral tablets)	Over-encapsulated Naltrexone (oral tablets)

Timeline

• Start date: 2026-05-01
• Primary completion: 2028-03-01
• Completion: 2028-06-01
• First posted: 2025-11-25
• Last updated: 2026-03-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study