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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001603-DA

Sponsoring Institute

National Institute on Drug Abuse (NIDA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 110 Years

Referral Letter Required

No

Population Exclusion(s)

Children;
Non-English Speaking;
Adults who are or may become unable to consent;
Pregnant Women

Keywords

Alcohol;
Pharmacotherapy;
GLP-1;
Semaglutide

Recruitment Keyword(s)

None

Condition(s)

Addiction;
Alcohol Use Disorder

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Behavioral: Take Control
Drug: Semaglutide

Supporting Site

National Institute on Drug Abuse

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 is safe and 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.

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Eligibility

INCLUSION CRITERIA:

This study will enroll adult individuals with a current diagnosis of AUD. Participants will be recruited without any preference to gender, 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 + 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 < 25 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 > 4(SqrRoot) 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


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Citations:

Lau J, Bloch P, Sch(SqrRoot) ffer 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.

Jensen L, Helleberg H, Roffel A, van Lier JJ, Bj(SqrRoot) rnsdottir I, Pedersen PJ, Rowe E, Derving Karsb(SqrRoot) l 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.

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; PMCID: PMC3415635.

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; PMCID: PMC4490279.

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. PMID: 33424537; PMCID: PMC7785877.

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; PMCID: PMC10371247.

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.

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; PMCID: PMC9338323.

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; PMCID: PMC8820218.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Lorenzo Leggio, M.D.
National Institute on Drug Abuse (NIDA)
NIH BIOMEDICAL RESEARCH CENTER BG RM 04A515
251 BAYVIEW BLVD.
BALTIMORE MD 21224
(240) 478-1503
lorenzo.leggio@nih.gov

Mehdi Farokhnia, M.D.
National Institute on Drug Abuse (NIDA)

(240) 852-9763
mehdi.farokhnia@nih.gov

Lorenzo Leggio, M.D.
NIH BIOMEDICAL RESEARCH CENTER BG RM 04A515
251 BAYVIEW BLVD.
BALTIMORE MD 21224
(443) 740-2801
lorenzo.leggio@nih.gov

Clinical Trials Number:

NCT06015893

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