Semaglutide (SEMA) for Alcohol Use Disorder (AUD) After Metabolic and Bariatric Surgery (MBS)

Official title

Semaglutide Treatment for Alcohol Use Disorder After Metabolic and Bariatric Surgery: A Pilot Randomized Controlled Trial

Overview

The purpose of this research study is to evaluate the feasibility of treating Alcohol Use Disorder with Semaglutide after metabolic and bariatric surgery in adults with overweight or obesity.

Detailed description

This study aims to evaluate the feasibility and acceptability of treating Alcohol Use Disorder with Semaglutide after metabolic and bariatric surgery in adults with overweight/obesity. This study will also examine changes in alcohol use disorder and weight. It is hypothesized that the treatment will be feasible and acceptable to participants, and result in reductions in alcohol use and weight.

A recently published randomized controlled trial provided preliminary evidence that Semaglutide can reduce some alcohol craving and drinking outcomes; however, this has not been examined in individuals with a history of bariatric surgery who are at increased risk of alcohol misuse and Alcohol Use Disorder.

Interventions

• Drug Semaglutide 1.0 mg
  Participants randomized to Semaglutide will be initiated on a 0.25 mg dose (injection) once weekly for 4 weeks (first month) with an escalation to 0.5 mg for the second month, and 1.0 mg in the final month (three months total).

Primary outcome measures

• Percent weight change [Time frame: Baseline, Week 12, 6-month follow-up]
• Mean drinks per calendar day to assess alcohol use [Time frame: Baseline, Week 4, Week 8, Week 12, 6-month follow-up]
• Mean drinks per drinking day to assess Alcohol use [Time frame: Baseline, Week 4, Week 8, Week 12, 6-month follow-up]
• Mean number of heavy drinking days to assess Alcohol use [Time frame: Baseline, Week 4, Week 8, Week 12, 6-month follow-up]
• Mean number of drinking vs abstinent days to assess Alcohol use [Time frame: Baseline, Week 4, Week 8, Week 12, 6-month follow-up]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study (up to 6 months: 3-month treatment plus 3-month follow up)
• Age 18 and older
• Have a BMI ≥30 (or BMI ≥27 with a medical comorbidity) and BMI ≤50 kg/m2
• Have had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy within the past seven years
• Meet current DSM-5 criteria for Alcohol Use Disorder
• Be an otherwise healthy subject without uncontrolled medical problems, as determined by the study physician and medical co-investigators
• Read, comprehend, and write English at a sufficient level to complete study-related materials
• For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation

Exclusion criteria

• Any of the following: myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack within the past 60 days prior to screening
• History or presence of chronic or recurrent pancreatitis
• History of malignant neoplasms within the past 5 years prior to screening
• Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
• Is currently using other medications for weight loss or other GLP-1 receptor agonists
• Has a history of allergy or sensitivity to Semaglutide
• Has a co-existing psychiatric condition that requires hospitalization or more intensive treatment (such as bipolar mood disorders, psychotic illnesses, or severe depression)
• Has untreated hypertension with a seated systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg, or heart rate > 100 beats/minute
• Has current uncontrolled hypertension
• Has current uncontrolled Type I or Type II diabetes mellitus
• Has untreated hypothyroidism with a TSH > 1.5 times the upper limit of normal for the test laboratory with repeat value that also exceeds this limit
• Has active gallbladder disease
• Has a history of severe renal, hepatic, neurological, chronic pulmonary disease, or any other unstable medical disorder
• Has a recent history of substance use disorder (with the exception of cannabis or tobacco use disorder) within the past 12 months
• Is currently engaging in other treatment for Alcohol Use Disorder or making intentional efforts to quit alcohol use
• Is currently participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug or device
• Is breast-feeding, pregnant, or not using a reliable form of birth control
• Reports active suicidal or homicidal ideation
• Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria which, in the investigator's opinion, might have jeopardized the participant's safety or compliance with the protocol

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Yale School of Medicine — New Haven

Publications

• Hendershot CS, Bremmer MP, Paladino MB, Kostantinis G, Gilmore TA, Sullivan NR, Tow AC, Dermody SS, Prince MA, Jordan R, McKee SA, Fletcher PJ, Claus ED, Klein KR. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Apr 1;82(4):395-405. doi: 10.1001/jamapsychiatry.2024.4789. PMID 39937469

Identifiers

NCT: NCT07223983 · 2000039710

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗