Semaglutide Therapy for Alcohol Reduction (STAR)

NCT06015893 | Recruiting Phase 2

• 2 other identifiers: 10001603001603-DA
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically significant medical consequences. Medications can help most people reduce their drinking, but the number is limited, and additional treatment options are needed. Objective: To test if a medication named Semaglutide may reduce alcohol drinking in people with AUD. Who can participate? All Adults aged 18 or older with AUD might be eligible to participate in the study. What will happen during the study? Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the tasks scheduled for that visit. Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide or placebo. A placebo looks just like a real drug but contains no medicine. The study medication is given as a shot under the skin each week. Participants will undergo different tests throughout the study: They will give blood, urine, and saliva samples. They will engage in self-paced behavioral therapy on a computer. They will answer questions about their mood, diet, alcohol drinking and craving, tobacco use, etc. They will taste several sweet liquids and tell their preferences. They will sit in a bar-like room and be exposed to cues that might make them feel the urge to eat food or drink alcohol. They will wear a virtual reality headset that creates a cafeteria setting. They will walk the virtual cafeteria and choose food and drinks from a buffet. They will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their brain. During the scans, participants will be shown pictures of alcohol-containing drinks, food, and other items.They will perform tasks on a computer screen. Participants will have a follow-up visit about 7 weeks after their last shot.

Conditions

Alcohol Use Disorder; Addiction

Keywords

Alcohol; Pharmacotherapy; GLP-1; Semaglutide

Outcome Measures

Primary Outcomes (1)

• Determine whether semaglutide, compared to placebo, reduces alcohol drinking.

  Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.

  Difference in number of standard alcohol-containing drinks consumed / week (Drinks Per Week, DPW) from baseline to end of the study.

Secondary Outcomes (6)

• Determine whether semaglutide reduces brain activity in resting-state and/or task-based fMRI scans.

  Difference in relevant fMRI measures between the two groups.

• Determine whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory.

  Difference in food selection in the virtual buffet between the two groups.

• Determine whether semaglutide reduces alcohol/food cue-elicited craving assessed in a bar-like laboratory.

  Difference in alcohol/food craving scores post exposure between the two groups.

• Determine whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use.

  Difference in blood PEth levels from baseline to end of the study.

• Determine whether semaglutide, compared to placebo, reduces other self-reported alcohol-related outcomes.

  Difference in other alcohol-related outcomes (e.g., heavy drinking days, drinks per drinking days, WHO drinking levels) from baseline to end of the study.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Weekly subcutaneous (s.c.) injections of placebo.

Behavioral: Take Control

Semaglutide

EXPERIMENTAL

Weekly subcutaneous (s.c.) injections of semaglutide up to 2.4 mg/week or maximum tolerated dose (MTD). Consistent with current recommendations, the dose will be titrated at minimum every four weeks to maximize tolerability and minimize adverse events.

Behavioral: Take Control; Drug: Semaglutide

Interventions

Semaglutide DRUG

Weekly subcutaneous (s.c.) injections of semaglutide (or placebo) up to 2.4 mg/week or maximum tolerated dose (MTD).

Semaglutide

Take Control BEHAVIORAL

A computer-delivered behavioral therapy derived from the NIAAA s self-help approach, Rethinking Drinking, developed for use in pharmacotherapy trials.

Placebo; Semaglutide

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

RECRUITING

Related Publications (9)

• Lau J, Bloch P, Schaffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015 Sep 24;58(18):7370-80. doi: 10.1021/acs.jmedchem.5b00726. Epub 2015 Sep 11.

  PMID: 26308095 BACKGROUND

• Jensen L, Helleberg H, Roffel A, van Lier JJ, Bjornsdottir I, Pedersen PJ, Rowe E, Derving Karsbol J, Pedersen ML. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41. doi: 10.1016/j.ejps.2017.03.020. Epub 2017 Mar 16.

  PMID: 28323117 BACKGROUND

• Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol. 2012 May;166(1):27-41. doi: 10.1111/j.1476-5381.2011.01687.x.

  PMID: 21950636 BACKGROUND

• Suchankova P, Yan J, Schwandt ML, Stangl BL, Caparelli EC, Momenan R, Jerlhag E, Engel JA, Hodgkinson CA, Egli M, Lopez MF, Becker HC, Goldman D, Heilig M, Ramchandani VA, Leggio L. The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence. Transl Psychiatry. 2015 Jun 16;5(6):e583. doi: 10.1038/tp.2015.68.

  PMID: 26080318 BACKGROUND

• Marty VN, Farokhnia M, Munier JJ, Mulpuri Y, Leggio L, Spigelman I. Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats. Front Neurosci. 2020 Dec 23;14:599646. doi: 10.3389/fnins.2020.599646. eCollection 2020.

  PMID: 33424537 BACKGROUND

• Chuong V, Farokhnia M, Khom S, Pince CL, Elvig SK, Vlkolinsky R, Marchette RC, Koob GF, Roberto M, Vendruscolo LF, Leggio L. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023 Jun 22;8(12):e170671. doi: 10.1172/jci.insight.170671.

  PMID: 37192005 BACKGROUND

• Farokhnia M, Browning BD, Crozier ME, Sun H, Akhlaghi F, Leggio L. The glucagon-like peptide-1 system is modulated by acute and chronic alcohol exposure: Findings from human laboratory experiments and a post-mortem brain study. Addict Biol. 2022 Sep;27(5):e13211. doi: 10.1111/adb.13211.

  PMID: 36001436 BACKGROUND

• Farokhnia M, Fede SJ, Grodin EN, Browning BD, Crozier ME, Schwandt ML, Hodgkinson CA, Momenan R, Leggio L. Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use. Sci Rep. 2022 Jul 29;12(1):13027. doi: 10.1038/s41598-022-17190-3.

  PMID: 35906358 BACKGROUND

• Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol. 2022 Feb;179(4):625-641. doi: 10.1111/bph.15677.

  PMID: 34532853 BACKGROUND

MeSH Terms

Conditions

Behavior, Addictive; Alcoholism

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Compulsive Behavior; Impulsive Behavior; Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Lorenzo Leggio, M.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Masoumeh Dejman

CONTACT

(240) 987-8983; masoumeh.dejman@nih.gov

Lorenzo Leggio, M.D.

CONTACT

(240) 478-1503; lorenzo.leggio@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: August 29, 2023
• Study Start: October 17, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05-04

Locations

US (1)