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Not yet recruitingNCT07249554Updated Jul 13, 2026

Combination Therapy for Alcohol Use Disorder

A Phase 2 interventional study of Placebo and Glucagon-Like Peptide-1 Agonist (GLP-1) in Alcohol Use Disorder, sponsored by Johns Hopkins University. Not yet recruiting at 1 site in United States. Open to participants aged 21 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-07-13.

Sponsored by Johns Hopkins University · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
21 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Alcohol Use Disorder

Keywords

  • Glucagon-like peptide 1
  • Naltrexone
  • Alcohol Use Disorder
  • Addiction
03

Who can participate

Ages eligible
21 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Aged 21-65 years old
  • Enrolled at Ashley Addiction Treatment center at least one week prior to beginning study participation.
  • Meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for Alcohol Use Disorder
  • Willing to comply with the study protocol

Exclusion criteria

Exclusion Criteria:

  • Score 9 or greater on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) at randomization
  • Currently pregnant, breastfeeding
  • Unwilling to use contraceptives (e.g., condoms and/or hormonal birth control)
  • Meet criteria for another substance use disorder other than AUD, Tobacco Use Disorder, or Caffeine use disorder
  • History of pancreatitis
  • History or current diagnosis of gallbladder disease, hepatic disease, renal disease, hyperparathyroidism, or any physical health condition that would be contraindicated with GLP-1 agonists or naltrexone.
  • Unmanaged diabetes diagnosis or history or current diagnosis of diabetic retinopathy
  • Levels of amylase, lipase, aspartate aminotransferase (AST), and/or alanine transferase (ALT) greater than 2x upper limit of normal
  • Personal or family history of medullary thyroid carcinoma given FDA box warning for semaglutide
  • Diagnosis of cancer within past 5 years
  • History of multiple endocrine neoplasia syndrome type 2 (MEN2)
  • Currently taking any medications contraindicated with GLP-1 agonists and/or naltrexone.
  • BMI \<18.5
  • Current elevated suicide risk as assessed by clinic staff or the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Any other medical or psychological condition that is judged by the investigators to impede ability to safely complete study requirements.
  • Legal problems or living situation judged by the investigators as a factor that could interfere with study completion (e.g., impending jail time).
  • Allergies to semaglutide and/or naltrexone
  • Use of opioids within the past 10 days as indicated by self-report or a positive urine drug screen
  • Prescribed or taking the following medications in the past four weeks:
  • The following medications will be prohibited during study participation due to interactions with semaglutide: other GLP-1 agonists (e.g. Exenatide, liraglutide, dulaglutide), insulin, insulin-secreting medications (e.g. sulfonylureas, meglitinides), tirzepetide, dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. sitagliptin, saxagliptin, linagliptin, alogliptin, evogliptin, and gemigliptin).
  • The following medications will be prohibited during study participation due to interactions with naltrexone: bremelanotide, peripherally-acting mu-opioid receptor antagonists (e.g. methylnaltrexone, naldemedine), and opioid agonist medications.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
45 participants (estimated)

Study arms

  • Placebo comparator
    Placebo+Placebo

    Placebo+Placebo

    Drug: Placebo

  • Experimental
    Placebo+GLP-1

    Placebo+GLP-1

    Drug: Placebo · Drug: Glucagon-Like Peptide-1 Agonist (GLP-1)

  • Experimental
    GLP-1+Naltrexone

    GLP-1+Naltrexone

    Drug: Glucagon-Like Peptide-1 Agonist (GLP-1) · Drug: Naltrexone (oral tablets)

Interventions

  • DrugPlacebo

    Over-encapsulated non-active microcrystalline cellulose

  • DrugGlucagon-Like Peptide-1 Agonist (GLP-1)

    Over-encapsulated Glucagon-Like Peptide-1 Agonist (GLP-1) oral tablets

  • DrugNaltrexone (oral tablets)

    Over-encapsulated Naltrexone (oral tablets)

05

What researchers measure

Primary outcomes

  1. Participant-reported Adverse Events

    Participant-reported adverse events during the course of the trial

    Time frame: 14 days

06

Study locations

1 site
  • Ashley Addiction Treatment
    Havre de Grace, Maryland 21078, United States
07

References and documents

Individual participant data

Plan to share: No — Data may be shared upon request.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07249554
Lead sponsor
Johns Hopkins University
Responsible party
Sponsor
First posted
Nov 25, 2025
Start date
Sep 2026 (estimated)
Primary completion
Jul 2028 (estimated)
Completion
Sep 2028 (estimated)
Last update
Jul 13, 2026

Study contacts

Andrew S Huhn, Ph.D.
Contact
ahuhn1@jhu.edu
410-550-1971
Breanna Labos, B.A.
Contact
blabos1@jhmi.edu
Andrew S. Huhn, Ph.D.
principal investigator · Johns Hopkins University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

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