Status:
NOT_YET_RECRUITING
Cessation or Reduction of Alcohol Consumption in Veterans: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of a GLP-1 Receptor Agonist Semaglutide in U.S. Veterans With Alcohol Use Disorder
Lead Sponsor:
VA Office of Research and Development
Conditions:
Alcohol Use Disorder
Eligibility:
All Genders
18-80 years
Phase:
PHASE3
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 ...
Detailed Description
AUD is one of the leading causes of disability worldwide. The prevalence of AUD is high, affecting 10.9% of US adults and 5.1% of adults worldwide. Oral naltrexone, the most widely prescribed medicati...
Eligibility Criteria
Inclusion
- Veteran.
- WHO risk drinking level of Very High or High in the 30 days prior to screening.
- Current diagnosis of moderate or severe AUD (i.e., meeting at least 4 of 11 DSM-5 AUD criteria) based on semi-structured diagnostic exam.
- Able and willing to provide informed consent.
Exclusion
- Medical and Psychiatric:
- Type 1 diabetes.
- Current serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, borderline or antisocial personality disorder, eating disorder).
- Current DSM-5 diagnosis of a SUD (other than moderate-to-severe alcohol, any nicotine, or mild cannabis use disorders).
- At the time of randomization, moderate-to-severe alcohol withdrawal (Clinical Institute Withdrawal Assessment for Alcohol (CIWA-AR) \>8).
- BMI \<21 kg/m2.
- Unstable body weight defined as \>5% change in body weight (documented or self-report; intentional or not) in the 90 days prior to randomization.
- 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 stage 3 fibrosis or stage 4 cirrhosis from a liver biopsy.
- Presence of gastroparesis.
- History of acute gallbladder disease in the prior 6 months.
- 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 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.
- History of autoimmune liver disease.
- History of hemochromatosis.
- History of Wilson's disease.
- History of alpha-10 antitrypsin-related liver disease.
- History of drug-induced liver disease.
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
- 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 Sub-Investigator (Sub-I), make it unlikely the participant can participate in or complete the 28-week active phase of the study.
- 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.
- Laboratory
- Hemoglobin A1c (HbA1c)\>10.
- Estimated glomerular filtration rate (eGFR) \<30 mL/min.
- Albumin \< 3.5 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/µL 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.
- Concurrent Treatments:
- Current (within the past 30 days) use of pharmacotherapy for AUD (including oral or intramuscular naltrexone, acamprosate, disulfiram, topiramate).
- Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue.
- 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 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).
- Other
- Pregnant, actively breastfeeding, or female of childbearing potential who is unwilling to use a highly effective method of contraception as defined by the NIH \[67\].
- Currently enrolled in another therapeutic or investigational clinical trial.
- Participant is incarcerated.
Key Trial Info
Start Date :
May 1 2026
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
May 26 2029
Estimated Enrollment :
438 Patients enrolled
Trial Details
Trial ID
NCT07218354
Start Date
May 1 2026
End Date
May 26 2029
Last Update
January 7 2026
Active Locations (1)
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1
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, United States, 19104-4551