NCT07218354 · VA Office of Research and Development
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
(CRAVE)
What this study is about
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 28-week period, followed by a 4-week post-treatment safety assessment period.
View original scientific description
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 28-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 effectiveness of semaglutide for treating AUD, potentially offering a new and more appealing treatment option.
Interventions
DRUG
Semaglutide
Weekly subcutaneous injections of semaglutide up to 2.4 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.
DRUG
Placebo
Weekly subcutaneous injections of placebo.
Primary outcome measures
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 to Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.
Number of participants with at least a two-level reduction, from baseline risk level, in WHO risk drinking level. The WHO risk drinking levels categorize alcohol consumption into four groups: low (level 1; 0-2.86 standard drinks/day for men; 0-1.43 drinks/day for women), moderate (level 2; 2.87-4.29 standard drinks/day for men; 1.44-2.86 drinks/day for women), high (level 3; 4.3-7.14 standard drinks/day for men; 2.87-4.29 drinks/day for women), and very high (level 4; \>7.15 drinks/day for men; \>4.3 drinks/day for women). One standard drink is 14 grams (g) of alcohol. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- WHO risk drinking level of Very High or High in the 28 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
- Has a desire to reduce their alcohol consumption
Exclusion criteria
- Medical and Psychiatric:
- Type 1 diabetes
- 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 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)
- Body mass index (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 alpha1 antitrypsin deficiency related liver disease
- Current 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 judgement 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
- 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, 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) 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
- Currently enrolled in another therapeutic or investigational clinical trial
- Participant is incarcerated
Where
- Long Beach, California
- Palo Alto, California
- West Los Angeles, California
- Orlando, Florida
- Decatur, Georgia
- Hines, Illinois
- Ann Arbor, Michigan
- Minneapolis, Minnesota
- Asheville, North Carolina
- Durham, North Carolina
- Cleveland, Ohio
- Portland, Oregon
And 6 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 4, 2026 · Source of record for eligibility and locations