Semaglutide Therapy for Alcohol Reduction (STAR)

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.

Timeline

Start

2023-10-17

Primary completion

2030-12-31

Completion

2030-12-31

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

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Indications