Clinical Trial of Rybelsus (Semaglutide) Among Adults With Alcohol Use Disorder (AUD)

Alcohol Use Disorder Clinical Trial

Official title:

Randomized, Controlled Trial of Rybelsus (Semaglutide) Among Adults With Alcohol Use Disorder (AUD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05892432
• Other study ID #: 23-0261
• Secondary ID: R21AA031146
• Status: Recruiting
• Phase: Phase 2
• Start date: January 11, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: University of Colorado, Denver
• Contact: Joseph P Schacht, PhD
• Phone: 303-724-3773
• Email: joseph.schacht[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized controlled trial of oral semaglutide among treatment-seeking individuals with AUD. The investigators will randomly assign 50 participants to receive semaglutide (titrated to 7 milligrams (mg) per day) or matched placebo for 8 weeks. The primary aims are to assess the safety and tolerability of semaglutide in this population and to evaluate its effects, relative to placebo, on alcohol cue-elicited craving and alcohol consumption.

Description:

A screening visit will be conducted at which written informed consent will be obtained and inclusion/exclusion criteria will be assessed. Subsequently, eligible participants will be randomly assigned to take oral semaglutide or matched placebo for 8 weeks, with the semaglutide dose titrated from 3 milligrams (mg)/day for the first 4 weeks to 7 milligrams (mg)/day for the second 4 weeks. Participants will complete 7 additional clinic visits (weekly during the first 4 weeks of the treatment period and biweekly during the second 4 weeks). At each visit, participants will also engage in a computerized behavioral intervention. At screening and again at the Week 6 visit, participants will complete an alcohol cue reactivity task. At the Week 1 visit, before ingesting the first dose of study medication, and again at the Week 8 visit, participants will complete a functional MRI session.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Age 21 or older.

2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current AUD of at least moderate severity, as assessed by the Mini International Neuropsychiatric Interview (MINI).

3. Seeking pharmacological treatment for AUD and wants to stop or cut down on drinking.

4. Has a body mass index (BMI) of at least 25 kg/m2.

5. Able to read and understand questionnaires and informed consent.

6. Lives within 50 miles of the study site.

Please contact clinical site for additional inclusion criteria.

Exclusion Criteria:

1. Current DSM-5 diagnosis of any other substance use disorder of moderate or greater severity, except for Nicotine Use Disorder, as assessed by MINI.

2. Urine drug screen at screening positive for any substance except cannabis.

3. Current DSM-5 bipolar disorder, major depressive episode, or panic disorder, as assessed by MINI.

4. Current or lifetime eating disorder (anorexia, bulimia, or binge eating disorder) or psychotic disorder, as assessed by MINI.

5. Current suicidal ideation or homicidal ideation.

6. Current use of other psychotropic medications except antidepressants (for which dose must be stable for at least the past 2 months).

7. Current or past-month use of AUD pharmacotherapy, including (e.g., oral naltrexone, acamprosate, or disulfiram) or current or past 60-day use of injectable naltrexone.

8. Current psychotherapy in which the primary focus is AUD. Attendance at Alcoholics Anonymous (AA) meetings is not exclusionary.

9. Current or past-month use of weight control medications.

10. Current or past-month use of metformin for any indication.

11. Any prior use of semaglutide or other GLP-1 agonists.

12. History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self- report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).

13. Current or lifetime Type 1 or Type 2 diabetes diagnosis, or HbA1c >6.5%.

14. Current or lifetime kidney disease or creatinine clearance <80 mL/min for participants <=55 years of age (<65 mL/min for those >55).

15. Personal history of gastrointestinal disease (e.g., gastroparesis) or pancreatitis.

16. Personal or family history of medullary thyroid carcinoma and/or multiple endocrine neoplasia syndrome type 2

17. Current or past hepatocellular disease, as indicated by verbal report or elevations of serum amylase, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of the normal range at screening.

18. Uncontrolled hypertension (systolic BP >160 mmHg or diastolic >100 mmHg).

19. Biological females of childbearing potential who are pregnant (by plasma HCG), nursing, or who are not using a reliable form of contraception.

20. Lack of a stable living situation.

21. (If participating in MRI sessions) Contraindications to MRI scanning, ferrous metal in the body including intracranial, intraorbital, or intraspinal metal, pacemakers, cochlear implants, other non-MRI-compatible devices, or other devices that could compromise the quality of the MRI images such as a permanent top retainer or braces.

22. (If participating in MRI sessions) Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

Drug:
• Semaglutide 3 MG [Rybelsus]
Semaglutide 3 mg will be taken for the first 4 weeks of the 8-week trial.
• Semaglutide 7 MG [Rybelsus]
Semaglutide 7 mg will be taken for the second 4 weeks of the 8-week trial.
• Placebo
A medically inert placebo medication will be taken for 8 weeks.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cue Craving Visual Analog Score	The primary efficacy endpoint will be the magnitude of change between screening and Week 6 in the cue-craving VAS score on the first VAS item ("How strong is your craving to drink alcohol?") administered after the alcohol cue presentation. Scores range from 0 (none) to 20 (extremely strong). Higher scores indicate a higher level of craving.	7 weeks - change between screening and Week 6 visit
Secondary	Number of drinks per day	The number of standard alcoholic drinks participants consume per day during the last 4 weeks of the treatment period (Week 5-8), as reported on the Timeline Follow-Back Interview.	4 weeks
Secondary	Percentage of heavy drinking days	The percentage of heavy drinking days during the last 4 weeks of the treatment period (Week 5-8), as reported on the Timeline Follow-Back Interview.	4 weeks