Using Semaglutide to Help Reduce Alcohol Consumption

Semaglutide Therapy for Alcohol Reduction (STAR): A Proof-of-Concept Phase II Clinical Trial

This study is testing if the medication Semaglutide can help adults with Alcohol Use Disorder drink less alcohol and manage their cravings better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 110 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06015893 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and early effectiveness of Semaglutide, a GLP-1 analogue, in reducing alcohol consumption among adults diagnosed with Alcohol Use Disorder (AUD). Participants will receive either Semaglutide or a placebo through weekly subcutaneous injections over a 20-week period, with assessments of alcohol intake and related outcomes conducted throughout. The study will also explore the impact of Semaglutide on cravings and other alcohol-related measures. The trial is designed as a Phase 2a pilot study to gather preliminary data on this potential new treatment option.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 or older who have a current diagnosis of Alcohol Use Disorder.

Not a fit: Patients who do not have a diagnosis of Alcohol Use Disorder or those who cannot communicate in English may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new pharmacotherapy option for individuals struggling with alcohol use disorder.

How similar studies have performed: While the use of GLP-1 analogues for alcohol reduction is a novel approach, other studies have shown promise in using pharmacotherapy for alcohol use disorder.

Eligibility criteria

* INCLUSION CRITERIA:

This study will enroll adult individuals with a current diagnosis of AUD. Participants will be recruited without any preference to sex, race, religion, or other social variables, but sociodemographic data will be collected for sample characterization and potential use in the analyses. Since self-reported psychological measures that have been validated in English constitute major part of the study assessments, participants need to be able to speak, read, write, and understand English to be in the study.

The information needed to assess eligibility will be collected under an IRB-approved NIDA IRP

screening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to assess

potential research participants' eligibility for entering clinical protocols. Additional details can be found in the NIDA screening protocol documents. Furthermore, NIH medical records (from other NIH clinical protocols) and outside medical records may also be used, if available, to determine whether participants fulfill the eligibility criteria.

To be eligible for this study, an individual must meet all of the following criteria:

* At least 18 years old
* Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID))
* Self-reported drinking, according to alcohol Timeline Follow-Back (TLFB), of \> 7 drinks per week for females or \> 14 drinks per week for males during the 28-day period prior to screening plus at least four days with \> 3 drinks for females or \> 4 drinks for males during the 28-day period prior to screening
* Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score \< 10
* Able to speak, read, write, and understand English as demonstrated by ability to understand and sign the NIDA screening protocol consent
* Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or corrected-to-normal (e.g., with the use of a hearing aid) hearing

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from enrolling in this study:

* BMI \< 23 kg/m\^2 or BMI \>= 50 kg/m\^2
* Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
* Most recent blood tests: creatinine \>= 2 mg/dL, eGFR \<45 mL/min/1.73 m\^2, triglycerides \> 500 mg/dl, ALP \> 4x the upper limit of normal, clinically abnormal lipase levels per study clinician
* Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) \>= 6.5 %
* Current (within the past 30 days) use of the following medications with glucose lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors
* Current or prior use of semaglutide or tirzepatide
* Current (within the past 30 days) use of weight-lowering medications
* Current (within the past 30 days) use of FDA-approved pharmacotherapy for AUD (oral or intramuscular naltrexone, acamprosate, disulfiram)
* Current (within the past 30 days) use of medications with known interaction with semaglutide
* Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
* Known ongoing history of alcohol ketoacidosis, gastroparesis, pancreatitis (either acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis
* Known history of gastric bypass surgery
* Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue
* Known history of suicidal attempts (within the past 24 months) or active suicidal ideation
* Known history of clinically significant vestibular disorders or motion sickness
* Known history of clinically significant noise-induced hearing loss or tinnitus
* Contraindication(s) for brain fMRI
* Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)
* Physical and/or mental health conditions that are clinically unstable, as determined by the study clinicians, including (but not limited to) major depressive disorder or generalized anxiety disorder unstable during the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the past twelve months prior to screening.
* Female who is pregnant, breast-feeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method
* Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant

Where this trial is running

Baltimore, Maryland

• National Institute on Drug Abuse — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Lorenzo Leggio, M.D. — National Institute on Drug Abuse (NIDA)
• Study coordinator: Masoumeh Dejman

Conditions Addiction; Alcohol Use Disorder; Alcohol; Pharmacotherapy; GLP-1; Semaglutide