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
CSP #2041 - 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)
1 other identifier
interventional
622
1 country
19
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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2026
Typical duration for phase_3
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2025
CompletedFirst Posted
Study publicly available on registry
October 20, 2025
CompletedStudy Start
First participant enrolled
July 28, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 30, 2030
August 4, 2026
July 1, 2026
2.7 years
September 23, 2025
July 31, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Two-level reduction in the World Health Organization (WHO) risk drinking level assessed in the last 28 days of intervention
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.
Change from Baseline to Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.
Secondary Outcomes (12)
Adverse events of special interest (Assessing safety and tolerability)
From randomization through week 32.
No heavy drinking days over the last 28 days of intervention.
Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.
Two-level reduction in the World Health Organization (WHO) risk drinking level by Race category during the last 56 days of the trial.
Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.
Two-level reduction in the World Health Organization (WHO) risk drinking level by age category (<65, ≥ 65) during last 28 days of intervention
Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.
Two-level reduction in the World Health Organization (WHO) risk drinking level by psychiatric comorbidity during last 28 days of intervention
Weeks 5-28. Includes six repeated measurements every 4 weeks from week 5 to 28.
- +7 more secondary outcomes
Study Arms (2)
Semaglutide
EXPERIMENTALWeekly 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.
Placebo
PLACEBO COMPARATORWeekly subcutaneous injections of placebo.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Veteran.
- 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
You may not qualify if:
- 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
- +39 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, 90822, United States
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, 94304-1207, United States
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
West Los Angeles, California, 90073-1003, United States
Orlando VA Healthcare System, Orlando, FL
Orlando, Florida, 32827, United States
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033-4004, United States
Edward Hines Jr. VA Hospital, Hines, IL
Hines, Illinois, 60141-3030, United States
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105-2303, United States
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309, United States
Asheville VA Medical Center, Asheville, NC
Asheville, North Carolina, 28805-2576, United States
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705-3875, United States
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106-1702, United States
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97207-2964, United States
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19104-4551, United States
Corporal Michael J. Crescenz VA Medical Center
Philadelphia, Pennsylvania, 19104, United States
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216-7167, United States
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030-4211, United States
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148-0001, United States
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108-1532, United States
William S. Middleton Memorial Veterans Hospital, Madison, WI
Madison, Wisconsin, 53705-2254, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
David W. Oslin, MD
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Participants assigned to the placebo group will receive a placebo pen, which mimics the treatment pens by following the same treatment procedure.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2025
First Posted
October 20, 2025
Study Start
July 28, 2026
Primary Completion (Estimated)
March 31, 2029
Study Completion (Estimated)
March 30, 2030
Last Updated
August 4, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
After the main results of this study have been published, de-identified data from the study may be shared with other VA investigators, other Federal health agencies, or academic institutions for the purpose of additional analyses provided this use has been approved by the appropriate VA oversight committee and there is an agreement in place that defines the limits of this use. Non-identified study data may be made available to the FDA and Novo Nordisk for medication approval.