Recruiting
Phase 3

Semaglutide

Sponsor:

VA Office of Research and Development

Code:

NCT07218354

Conditions

Alcohol Use Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Semaglutide

Placebo

Study Details

Brief summary:

This clinical trial aims to test the effectiveness and safety of semaglutide, a GLP-1 receptor agonist, in treating moderate to severe alcohol use disorder (AUD) in Veterans. Participants who qualify will be randomly assigned to receive either semaglutide injections or placebo injections over a 24-week period, followed by a 4-week post-treatment safety assessment period. Participants receiving semaglutide will start with a low dose, gradually increasing to a maximum of 2.4 milligrams (mg) per week, depending on their tolerance. The primary measure of success will be a reduction in risky drinking, assessed through a reliable calendar-based interview method called the Timeline Follow-Back (TLFB), a well-validated calendar-based interview technique for recording daily alcohol consumption. The purpose of this research is to gather information on the safety and effectiveness of semaglutide for treating AUD, potentially offering a new and more appealing treatment option.

Conditions

Alcohol Use Disorder

Study ID

NCT07218354

Start date

Jul 28, 2026

Status verified date

Sep, 2026

Completion date

Mar 30, 2030

Anticipated

Primary completion date

Mar 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Veteran
  • World Health Organization's (WHO) risk drinking level of Very High or High in the 28 days prior to screening (based on screening TLFB)
  • Current diagnosis of moderate or severe alcohol use disorder (AUD), i.e., meeting at least 4 of 11 DSM-5 AUD criteria, based on semi-structured diagnostic exam, the Mini-International Neuropsychiatric Interview (MINI)
  • Able and willing to provide informed consent
  • Has a desire to reduce their alcohol consumption

Exclusion Criteria:

  • Medical History (medical history form)

  • Type 1 diabetes
  • History of acute or chronic pancreatitis
  • History of diabetic ketoacidosis
  • History of proliferative diabetic retinopathy
  • History of ascites, advanced liver fibrosis, compensated cirrhosis with portal hypertension, decompensated cirrhosis, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatocellular carcinoma (HCC)
  • History of advanced fibrosis or cirrhosis, including (but not limited to) transient elastography (liver stiffness) of >12 kPa, FIB-4 ≥2.67, ELF ≥9.8, MRE ≥3.63 kPa
  • History of stage 3 fibrosis or stage 4 cirrhosis from a liver biopsy
  • History of esophageal varices on endoscopy or imaging
  • History of nodular liver, cirrhosis, splenomegaly, varices or splenic venous shunting or collaterals on prior imaging
  • History or acute alcohol hepatitis (by liver biopsy or elevated bilirubin > 1.5 times the upper limit of normal)
  • History of primary biliary cholangitis
  • History of primary sclerosing cholangitis
  • Current drug-induced liver disease
  • History of alpha1 antitrypsin deficiency related liver disease
  • History of autoimmune liver disease
  • History of hemochromatosis
  • History of Wilson's disease
  • Presence of gastroparesis
  • History of acute gallbladder disease in the prior 6 months
  • Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)
  • Unstable body weight defined as >5% change in body weight (documented or self-report; intentional or not) in the 90 days prior to randomization
  • Recent major cardiovascular event in the 90 days prior to randomization (myocardial infarction, stroke, New York Heart Association class IV heart failure, transient ischemic attack (TIA), or unstable angina
  • Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue
  • Concurrent Treatments (medical history form):

  • Current (within the past 30 days) use of pharmacotherapy for alcohol use disorder (AUD), including oral or intramuscular naltrexone, acamprosate, disulfiram, topiramate
  • Current (within the past 30 days) use of the following medications with glucose-lowering properties: GLP-1 analogues; sulfonylurea; insulin and insulin products; dipeptidyl peptidase-4 (DPP-4) inhibitors; sodium-glucose cotransporter-2 (SGLT-2) inhibitors, meglitinides, thiazolidinediones or other medications that may interact with semaglutide
  • Recent changes in dose (within 2 months of randomization) of psychiatric medications (i.e., antidepressants, antianxiety, mood stabilizing)
  • Psychiatric diagnosis, the Mini-International Neuropsychiatric Interview (MINI)

  • Current serious psychiatric illness (any psychotic disorder, bipolar 1 disorder, psychotic major depression, antisocial personality disorder, bulimia, or anorexia)
  • Current DSM-5 diagnosis of a Substance use disorder (SUD), other than moderate-to-severe alcohol, any nicotine, or mild cannabis use disorders
  • Other assessments (local site)

  • At the time of randomization, moderate-to-severe alcohol withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-AR) >8)
  • Body mass index (BMI) <21 kilograms/square meter (kg/m2)
  • Acute high risk of suicide requiring hospitalization at the time of screening or randomization
  • Medical, psychiatric, behavioral, or logistical conditions which, in the judgment of the Local Site Investigator (LSI) or Co-Investigator (Co-I), make it unlikely the participant can participate in or complete the 24-week active phase of the study
  • Pregnant, actively breastfeeding, or female of childbearing potential who is unwilling to use a highly effective method of contraception as defined by the NIH
  • Currently enrolled in another therapeutic or investigational clinical trial without a preexisting dual enrollment agreement
  • Participant is incarcerated
  • Laboratory

  • Hemoglobin A1c (HbA1c)>10
  • Estimated glomerular filtration rate (eGFR) <30 milliliters/minute (mL/min)
  • Albumin < 3.5 grams/deciliter (g/dl)
  • Aspartate aminotransferase (AST) >3 the Upper Limit of Normal (ULN)
  • Alanine aminotransferase (ALT) >3 the ULN
  • Lipase > 2 times the upper limit of normal
  • Alkaline phosphatase > 1.5 times the ULN
  • Total bilirubin > 1.5 times the ULN except with documented Gilbert's syndrome
  • International Normalized Ratio (INR) > 1.3 unless due to anticoagulation therapy
  • Platelet count <150,000/ liter (L) unless consistent with baseline and reflects the participant's habitual thrombocyte level, and there was no presence of portal hypertension
  • Hepatitis B surface antigen positive
  • Hepatitis C virus RNA positive - participants treated and cured of hepatitis C must have at least 2 years of negative testing
  • Anti-HIV antibody positive test with uncontrolled or unstable treatment
  • Positive urine drug screen for substances other than cannabis and prescribed medications
  • Positive urine pregnancy test at screening in those considered of childbearing potential

Study Design

Enrollment

622 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Semaglutide

Weekly subcutaneous injections of semaglutide up to 2.4 milligram (mg)/week or maximum tolerated dose. Initial dosing starting at 0.25 for weeks 1-4. Further titration up to 2.4 mg weekly starting at week 5.

placebo comparator: Placebo

Weekly subcutaneous injections of placebo mimicking treatment procedure.

Interventions

Semaglutide

Weekly subcutaneous injections of semaglutide up to 2.4 milligram (mg)/week or maximum tolerated dose. Initial dosing starting at 0.25 for weeks 1-4. Further titration up to 2.4 mg weekly starting at week 5.

Placebo

Weekly subcutaneous injections of placebo mimicking treatment procedure.

Primary outcome measure

  • Two-level reduction in the World Health Organization (WHO) risk drinking level assessed in the last 28 days of intervention [ Time Frame: Change from baseline (after randomization) to change in the last 28 days of the intervention ]

Central Contacts and Locations

Central contacts

David W Oslin, MD

(215) 823-5894Dave.Oslin@va.gov

Neil C Johnson, MA BA

neil.johnson@va.gov

Locations

VA Long Beach Healthcare System, Long Beach, CA

Recruiting

Long Beach, California, United States, 90822

Contacts

Larry Albers, MD

562-826-8000larry.albers@va.gov

Sakineh Khalaghizadeh(Parvin)

5628268000sakineh.khalaghizadeh@va.gov

VA Palo Alto Health Care System, Palo Alto, CA

Recruiting

Palo Alto, California, United States, 94304-1207

Contacts

Michael J Ostacher, MD

650-493-5000Michael.Ostacher@va.gov

Audrey Fish, BA

6504935000audrey.fish@va.gov

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Recruiting

West Los Angeles, California, United States, 90073-1003

Contacts

Zhaoping Li, MD

310-268-3528zhaoping.li@va.gov

Michelle Treadwell

3108067162michelle.treadwell@va.gov

Orlando VA Healthcare System, Orlando, FL

Recruiting

Orlando, Florida, United States, 32827

Contacts

Ishak Mansi, MD

407-631-4011Ishak.mansi@va.gov

Pedro Rivera Velez

4076077378pedro.riveravelez@va.gov

Edward Hines Jr. VA Hospital, Hines, IL

Recruiting

Hines, Illinois, United States, 60141-3030

Contacts

Alma Ramic, MD

708-202-8387alma.ramic2@va.gov

Laurica Petrella-Zitko, BS

7089730757laurica.petrella-zitko@va.gov

VA Ann Arbor Healthcare System, Ann Arbor, MI

Recruiting

Ann Arbor, Michigan, United States, 48105-2303

Contacts

Ponni Perumalswami, MD

734-845-5345ponni.perumalswami@va.gov

Andrea Birkhofer, MPH

7344506026Andrea.Birkhofer@va.gov

Minneapolis VA Health Care System, Minneapolis, MN

Recruiting

Minneapolis, Minnesota, United States, 55417-2309

Contacts

Eric Dieperink, MD

Eric.Dieperink@va.gov

Sara Kemmer

6124671580Sara.kemmer@va.gov

Asheville VA Medical Center, Asheville, NC

Recruiting

Asheville, North Carolina, United States, 28805-2576

Contacts

Brandon Corbett, MD

brandon.corbett@va.gov

Kathy Betts

8282987911kathleen.betts@va.gov

Durham VA Medical Center, Durham, NC

Recruiting

Durham, North Carolina, United States, 27705-3875

Contacts

Daniel Blalock, MD

Daniel.Blalock@va.gov

Madison Setzer

Madison.Setzer@va.gov

Louis Stokes VA Medical Center, Cleveland, OH

Recruiting

Cleveland, Ohio, United States, 44106-1702

Contacts

Michael Ignatowski, MD

216-231-3241

Amy Bondsteel

2162313241

VA Portland Health Care System, Portland, OR

Recruiting

Portland, Oregon, United States, 97207-2964

Contacts

Kyle Sears, MD

503-273-5108kyle.sears@va.gov

Lorrinda Zahl

5032208262Lorrinda.Zahl@va.gov

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4551

Contacts

David W Oslin, MD

(215) 823-5894Dave.Oslin@va.gov

Corporal Michael J. Crescenz VA Medical Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Kyle Kampman, MD

Kyle.Kampman@va.gov

Christen Holmes

2158235800Christen.Holmes2@va.gov

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Recruiting

Dallas, Texas, United States, 75216-7167

Contacts

Kyaw Soe, MD

214-857-0125kyaw.soe@va.gov

Jodie-Ann Clarke

2148570393jodie-ann.clarke@va.gov

Michael E. DeBakey VA Medical Center, Houston, TX

Recruiting

Houston, Texas, United States, 77030-4211

Contacts

Christopher Verrico, PhD

713-798-7658Christopher.Verrico@va.gov

Adetola Vaughan, MPH

8327794803Adetola.Vaughan@va.gov

VA Salt Lake City Health Care System, Salt Lake City, UT

Recruiting

Salt Lake City, Utah, United States, 84148-0001

Contacts

Adam Gordon, MD

385-297-0370Adam.Gordon@va.gov

Dianna Fuessel-Herrmann

Dianna.FuesselHerrmann@va.gov

VA Puget Sound HCS - Seattle and Tacoma

Recruiting

Tacoma, Washington, United States, 98493

Contacts

SueAnn Brickle

253-583-2026sueann.brickle@va.gov

Deepika Agrawal, MD

2535832026deepika.agrawal@va.gov

William S. Middleton Memorial Veterans Hospital, Madison, WI

Recruiting

Madison, Wisconsin, United States, 53705-2254

Contacts

Timothy Juergens, MD

608-280-7084Timothy.juergens@va.gov

Nicole Rafidi, MS

6082561901nicole.rafidi@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Sep 21, 2026

Last verified

Sep, 2026

Keywords

  • Alcohol Use Disorder
  • Semaglutide
  • Alcohol
  • GLP-1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-09-21. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.