A Phase 3 interventional study of Semaglutide and Placebo in Alcohol Use Disorder, sponsored by VA Office of Research and Development. Recruiting at 19 sites in United States. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by VA Office of Research and Development · Phase 3, Interventional, and Treatment
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Among 11 studies testing semaglutide in Alcoholism — 5 open to participants now, 7 under way, 1 of them phase 3. Semaglutide · Alcoholism.
Among the 11 studies testing semaglutide in Alcoholism, this one has the largest planned enrollment, is one of 6 that started in 2026, is the only one in phase 3, and was the 8th registered.
1,676 studies on the registry are indexed under Alcoholism; 331 are open to participants now.
Browse Alcoholism studies →5 of the 11 studies testing semaglutide in Alcoholism are open now, in 2 countries. Recruiting first, the newest first:
Yale University · Sites in United States
Ages 18–68
Yale University · Sites in United States
Ages 18–99
Insel Gruppe AG, University Hospital Bern · Sites in Switzerland
Ages 18–80
Johns Hopkins University · Sites in United States
Ages 21–65
By country, each count listing its studies:
Semaglutide: first FDA approval 2017 (OZEMPIC), first EMA approval 2018. What it is approved for, and how studies give it, is on its page →
Of the 237 Alcoholism studies recruiting now, 84 (35%) set no upper age limit and 131 (55%) stop at 75 or younger; 9 take children under 18; 64 take healthy volunteers.
This study: 18 Years to 80 Years · all sexes · healthy volunteers too.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
On this site’s reading of the record, semaglutide is the treatment under test here. Read study by study →
11 studies; the count open now beside each. This study's row is marked.
First in 2022; this study’s year is marked. 6 started in 2026.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 622 is above the median of 88 across 1,430 interventional studies indexed under Alcoholism.
Median enrollment 63 across the 11 interventional studies. Of the 4 that completed or were terminated, 1 (25%) have results posted.
This tab as a report to print or save as PDF → With an account.
None of the 11 has an industry lead sponsor. The 9 most frequent:
VA Office of Research and Development is the lead sponsor of 1,773 studies on the registry; 393 are open to participants now.
Of its 213 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.
47 studies in Alcoholism by VA Office of Research and Development: 7 open now, 9 under way, 2 of them phase 3. Of 37 finished, 33 (89%) have results posted.
Among the 47 studies in Alcoholism by VA Office of Research and Development, this one is the 2nd largest by planned enrollment of the 42 interventional ones that give a count, is one of 2 that started in 2026, is one of 3 in phase 3, and was the 46th registered.
VA Office of Research and Development’s Alcoholism studies by the year they started, since 2005.
4 of the studies testing semaglutide in Alcoholism that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06546384Insel Gruppe AG, University Hospital BernGLP-1 RA on Alcohol Consumption, Metabolism and Liver Parameters in Patients With Obesity and Fatty Liver Disease | 2026-12-31 |
| NCT07223983Yale UniversitySemaglutide (SEMA) for Alcohol Use Disorder (AUD) After Metabolic and Bariatric Surgery (MBS) | 2027-02 |
| NCT06015893National Institute on Drug Abuse (NIDA)Semaglutide Therapy for Alcohol Reduction (STAR) | 2027-03-31 |
| NCT07040592Yale UniversityOff-Label Medications for Alcohol Use Disorder Among Patients With HIV: Pilot Study 3 Semaglutide | 2027-06-30 |
Add all 4 to your calendar (.ics) → With an account.
Among the 11 studies testing semaglutide in Alcoholism, from their registry updates:
Among VA Office of Research and Development’s 47 in Alcoholism:
This tab as a report to print or save as PDF → With an account.
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.
Background:
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 medication for AUD, has a number needed to treat (NNT) to prevent a return to heavy drinking of 12, and thus is only modestly effective. Indeed, less than 2% of adults with AUD receive medication in a given year. Though the Department of Veterans Affairs promotes pharmacotherapy as a best practice, there are over 400,000 Veterans within the Veterans Health Administration (VHA) who have a diagnosis of AUD, with only about 40,000 being actively treated with pharmacotherapy (source: VA Quality Dashboard accessed 1/31/2025). As there have been no new Food and Drug Administration (FDA) approved medications in nearly two decades, there is an urgent need for novel treatments for AUD with superior efficacy and higher patient appeal. Based upon very promising clinical experience, retrospective studies, preclinical data, and recent pilot clinical trial results, the proposed clinical trial is designed to provide definitive evidence regarding the efficacy of the GLP-1 RA, semaglutide, compared to placebo for the treatment of AUD. This research will offer urgently needed information on the efficacy of GLP-1 RAs in the treatment of AUD in a diverse sample and is directly in line with the strategic priorities (SP) for VA Research codified by the Office of Research and Development (ORD) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
Study Design:
This is a randomized, double-blinded, intent-to-treat, two-arm, parallel, superiority multisite clinical trial in which 622 participants will be randomized into the semaglutide treatment or placebo arm in a 1:1 ratio. Randomization will be stratified according to BMI (\<30 or ≥ 30) and participating site. Veterans with DSM-5-diagnosed moderate to severe AUD who are seeking treatment will be invited to participate in this trial. After eligibility screening, participants will be randomized to either the semaglutide group or the placebo group.
The study will be conducted in three phases. Phase 1 will be Recruitment, Consent and Screening, Phase 2 will be Randomization and Intervention (6 months of treatment), which includes dose escalation and the primary endpoint ascertainment period (the last 28 days of the intervention period), and Phase 3 is the Post Treatment Safety Assessment (4 weeks).
Study Objectives:
Primary Objective: To evaluate the efficacy of semaglutide 2.4 mg compared to placebo in achieving the World Health Organization's (WHO) two-level alcohol risk reduction (WHO-2LRR), from baseline risk level, in the WHO risk drinking level in the treatment of moderate to severe AUD. The primary outcome will be measured during the last 28 days of the intervention period.
Secondary Objectives:
Exploratory Objectives:
The following objectives aim to provide a comprehensive assessment of semaglutide's impact on various aspects of patients' well-being and recovery from AUD, compared to placebo:
Psychiatric Distress as measured by
Intervention and Masking:
Participants assigned to the semaglutide 2.4 mg group will undergo 24 weeks of treatment (Phase 2). Phase 2 will be used to initiate a dose of 0.25 mg with further dose escalation up to 2.4 mg weekly starting at week 5. Participants will be increased to their maximal tolerable dose. Increases will be considered only after the participant has been on the current dose for 4 weeks (dose escalation schedule is 0.25, 0.5, 1.0, 1.7, and 2.4 mg). Doses are not to exceed 2.4 mg weekly. Patients may have their dose reduced, maintain their current dose, or have a slower dose escalation to ensure tolerability and increase retention in the study. Doses are delivered via a pen, a cartridge-based device that calibrates medication delivery based on the desired dose. An extremely small needle (4-mm, 32-gauge needle - the size of 2 human hairs) is used to deposit the medication subcutaneously. Participants assigned to the placebo group will receive a placebo that mimics the same treatment procedure.
Throughout the study, the investigators will maintain double-blind conditions regarding the medication condition. To enhance the ability to maintain blinded assessment of the primary outcome, the assessment will be collected by a Central Assessment Center.
Sample Size and Study Duration:
This study plans to randomize 622 Veterans, with 311 participants assigned to each group. The study duration will be minimally 47 months for study start-up, approximately 32 months for recruitment, dose escalation, endpoint assessment and follow-up for safety, three months for data cleaning, and nine months for data analysis and reporting.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Medical History (medical history form)
Concurrent Treatments (medical history form):
Psychiatric diagnosis, the Mini-International Neuropsychiatric Interview (MINI)
Other assessments (local site)
Laboratory
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Semaglutide
Weekly subcutaneous injections of placebo mimicking treatment procedure.
Drug: Placebo
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.
Weekly subcutaneous injections of placebo mimicking treatment procedure.
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 or approximately 12oz beer, 5oz wine, or 1.5oz of liquor. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.
Time frame: Change from baseline (after randomization) to change in the last 28 days of the intervention
Adverse events of special interest (assessment of safety and tolerability)
Safety and tolerability will be assessed by comparing the proportion of participants experiencing an adverse event of special interest (AESI) in the semaglutide 2.4 mg treatment group versus placebo group.
Time frame: From randomization through week 32.
No heavy drinking days over the last 28 days of intervention
Proportion of subjects with no heavy drinking days. Heavy drinking is defined as \>4 standard drinks in a day for men and \>3 for women. This endpoint will be measured per participant self-report using timeline follow back methods.
Time frame: Change from baseline (after randomization) to change in the last 28 days of the intervention
Two-level reduction in the World Health Organization (WHO) risk drinking level assessed in the last 56 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 or approximately 12oz beer, 5oz wine, or 1.5oz of liquor. A 2-level reduction, such as moving from very high to moderate risk, is considered a significant clinical improvement.
Time frame: Change from baseline (after randomization) to change in the last 56 days of the intervention
Moderation effects of baseline characteristics
Baseline characteristics such as race, age, psychiatric comorbidity, psychiatric treatment, and impulsivity will be assessed for moderation on semaglutide treatment effects on the endpoints of at least a WHO-2LRR and NHDD, which will help to address generalizability of study findings.
Time frame: Change from baseline (after randomization) to change in the last 28 days of the intervention
Repeated measures assessment of primary and NHDD secondary outcomes
Repeated measures assessment of the primary outcome (proportion of subjects with WHO-2LRR) and a secondary outcome (proportion of subjects with NHDD) for each month over the entirety of the trial.
Time frame: Randomization to week 24.
Clinical Global Impression-Improvement (CGI-I)
CGI-I scale is a clinician-rated tool designed to assess treatment response and the efficacy of interventions in clinical studies of patients with mental disorders including AUD, which assesses how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention with a Likert scale ranging from 1 (very much improved) to 7 (very much worse). The CGI-I will be measured at the end of the ascertainment phase.
Time frame: End of ascertainment phase.
Quality of Life (QoL)
Quality of life will be assessed using the Veterans RAND-12 (VR-12), which is a 12-item self-administered instrument used to measure health-related quality of life. The 12 items in the questionnaire correspond to eight principal physical and mental health domains, which are summarized into two scores, a physical health summary measure (PCS-physical component score) and a mental health summary measure (MCS-mental component score). These provide an important contrast between physical and psychological health status. Each VR-12 item response will be coded numerically (e.g., 1-5 or 1-6), then transformed to a score on a 0-100 scale. The transformed PCS score (PCS\_T) and MCS score (MCS\_T) are summations of products of the transformed scores.
Time frame: Difference between baseline and end of the treatment.
Brief Addiction Monitor - Revised (BAM-R)
The BAM-R, a structured instrument of multidimensional clinical outcome monitoring progress in addiction treatment, has three domains of substance use (alcohol and drug use frequency, craving), risk factors (sleep, mood, housing instability, legal issues), and protective factors (recovery supports, abstinence confidence, self-help participation). Each item is scored on a 5-point Likert scale (0-4). The subscore ranges of the three domains are 0-12 for substance use, 0-28 for risk factors, and 0-16 for protective factors. The BAM-R will be self-reported at each visit, and the three subscores will be analyzed for improvements over time by treatment groups.
Time frame: The change in BAM-R will be measured over the 24-week ascertainment period.
Alcohol Craving
Alcohol craving will be assessed using the Penn Alcohol Craving Scale (PACS), which is a self-reported five-item questionnaire with each item scored from 0 to 6, measuring the frequency of thoughts about drinking, intensity of cravings, duration of cravings, ability to resist drinking, and overall craving rating over the past week. The total score ranges from 0 to 30.
Time frame: The endpoint will analyze a reduction in craving over the 24-week ascertainment period.
Psychiatric Distress
Psychiatric distress will be assessed using three instruments: the Patient Health Questionnaire-9 (PHQ-9), which is a self-administered instrument of 9 items, each corresponding to one of the DSM-5 criteria for major depressive disorder with a total score from 0 to27; the Generalized Anxiety Disorder-7 (GAD-7), which is a 7-item self-reported questionnaire (each item rated on a 4-point scale from 0 to 3) with a total score range of 0 to 21; and the PTSD Checklist for DSM-5 (PCL-5), which is a self-reported 20-item checklist measure, each corresponding to one DSM-5 PTSD symptom rated on a 5-point scale (0-4) with a total score range from 0 to 80. The following table summarizes key information on the three instruments, including score range, clinical categorization, and minimal clinically important difference (MCID).
Time frame: These will be measured over the 24-week ascertainment period.
Alcohol-Related Problems
Alcohol-related consequences and problems will be assessed using the Short Inventory of Problems (SIP-2R), which is a 15-item self-report questionnaire that includes five subdomains (i.e., physical, interpersonal, intrapersonal, impulse control, social responsibility). Each SIP-2R item is rated on a 4-point Likert scale from 0 to 3. Total SIP-2R score is the sum of all 15 items, with a score range of 0-45, and each subdomain score ranges from 0-9. Higher SIP-2R scores indicate more severe alcohol-related problems.
Time frame: The SIP-2R will be measured over the 24-week ascertainment period.
Health Care Utilization (HCU)
HCU provides critical context on how the treatment impacts medical resources and is assessed via four HCU domains, including emergency department (ED) visits, outpatient services, inpatient services, and other services. The investigators will examine HCU using VA electronic health record (EHR) data supplemented with an HCU supplemental self-report of services used outside of VA.
Time frame: The HCU frequency and types will be analyzed over the intervention period. In addition, consent will allow future examination of VA HCU for up to 3 years.
Plan to share: Yes — 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.
Supporting information: Study protocol, Statistical analysis plan
Time frame: Outlined in study documentation.
Access criteria: Outlined in study documentation.
No publications or documents are linked to this record.
Started Jul 2026 (actual). Primary completion is estimated for Mar 2029, 32 months after the start.
Of 25 phase 3 interventional studies under Alcoholism, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 54. This study's planned 32 months is below that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Semaglutide
VA Office of Research and Development →