Semaglutide Therapy for Alcohol Reduction - Tulsa (STAR-T)

• ClinicalTrials.gov Identifier: NCT05891587
• Recruitment Status: Recruiting
• First Posted: June 7, 2023
• Last Update Posted: November 7, 2023
• Sponsor: Oklahoma State University Center for Health Sciences
• Collaborator: National Institute of Drug Abuse
• Information provided by (Responsible Party): Oklahoma State University Center for Health Sciences

Tracking Information

• First Submitted Date: May 4, 2023
• First Posted Date: June 7, 2023
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: July 7, 2023
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2023)

Change in alcohol drinking [ Time Frame: Baseline (Week 1) to post-medication (Week 13 ]

Difference in number of standard alcoholic drinks consumed/week (Drinks Per Week, DPW)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 5, 2023)

• Change in heavy drinking days [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Difference in number of heavy drinking days as reported in Alcohol TLFB
• Change in drinks per drinking days [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Difference in number of drinks per drinking days as reported in Alcohol TLFB
• Safety and tolerability of semaglutide in individuals with alcohol use disorder (AUD) [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Number and grade of adverse events in individuals with AUD who receive semaglutide or placebo
• Reduction and/or changes in food choices in a virtual reality buffet-like laboratory [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Difference in the macronutrient content selected in the virtual reality buffet
• Change in blood phosphatidylethanol (PEth) levels as a biomarker of alcohol use [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Difference in blood PEth levels
• Changes in brain activity in response to alcohol cues during fMRI cue reactivity task [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Group differences in fMRI blood oxygenation level dependent (BOLD) signal within reward neurocircuitry in response to alcohol and nonalcoholic beverage stimuli
• Changes in brain activity during an fMRI interoceptive attention task [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Group differences in fMRI blood oxygenation level dependent (BOLD) signal within interoceptive brain regions during an interoceptive attention task.
• Changes in brain activity during an alcohol-related Go/No-Go fNIRS task [ Time Frame: Baseline (Week 1) to post-medication (Week 13) ]
  Difference in activity of inhibitory brain regions during an alcohol-related Go/No-Go fNIRS task.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Semaglutide Therapy for Alcohol Reduction - Tulsa
• Official Title: Semaglutide Therapy for Alcohol Reduction - Tulsa
• Brief Summary: The purpose of this research study is to determine if semaglutide, when compared to placebo, is safe and may reduce alcohol drinking in individuals who endorse symptoms consistent with alcohol use disorder.
• Detailed Description: This is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and tolerability of semaglutide in individuals who meet criteria for alcohol use disorder. Participants will complete a remote phone screening and an on-site screening visit to determine study eligibility. Eligible participants will be randomized to receive weekly subcutaneous injections of either semaglutide or a placebo (1:1 ratio). Doses will be titrated according to the FDA-approved dosing schedule starting at a dose of 0.25 mg/week for four weeks, then 0.5 mg/week for four weeks, and finally the dose will be increased to 1.0 mg/week for four weeks, for a total of 12 weeks of treatment. Participants will be asked to complete experimental procedures at the baseline and endpoint visits (Week 1 and Week 12), which include functional magnetic resonance imaging (fMRI) experiments, functional near-infrared spectroscopy (fNIRS) experiments, and virtual reality experiments. Participants will also complete questionnaires, biospecimen collections, and computer-based behavioral therapy modules at various study timepoints. Participants will periodically meet with a study physician and will be monitored for any adverse events. A remote follow-up assessment will take place 9 weeks after the participant's last dosing visit.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, between-subject, double-blind, and placebo-controlled.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Alcohol Use Disorder

Intervention

• Drug: Semaglutide
  Semaglutide pen injector
• Drug: Placebo
  Saline solution

Study Arms

• Experimental: Semaglutide
  Participants will receive subcutaneous injections of semaglutide in escalating doses (.25mg to 1.0mg) over the course of 12 weeks.
  Intervention: Drug: Semaglutide
• Placebo Comparator: Placebo
  Participants will receive subcutaneous injections of a placebo saline solution over the course of 12 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 5, 2023): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Ability to provide informed consent before any trial-related activities
2. Male or female individuals who are at least 18 years old
3. Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., DSM-5 Checklist for Alcohol Use Disorder, the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID))
4. 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.
5. Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is ≤ 10
6. Able to speak, read, write, and understand English
7. 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
8. Female participants must be postmenopausal for at least one year, surgically sterile, or practicing a highly effective method of birth control before entry and throughout the study and must have a negative urine pregnancy test at each visit. Examples of birth control methods include (but are not limited to) oral contraceptives or contraceptive implants, barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms, intrauterine devices, a partner with a vasectomy, or abstinence from intercourse.

Exclusion Criteria:

1. BMI < 25 kg/m2 or BMI ≥ 50 kg/m2
2. Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
3. Most recent blood tests: creatinine ≥ 2 mg/dL, eGFR ≤ 60 mL/min/1.73 m2, triglycerides > 500 mg/dl, ALP > 4x the upper normal limit, abnormal blood lipase levels
4. Present diagnosis of diabetes or blood hemoglobin A1c (HbA1c) ≥ 6.5 %
5. Current use of the following medications with glucose lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones (TZD), dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors
6. Current or prior use of semaglutide (Ozempic or Wegovy) or tirzepatide (Mounjaro).
7. Use of weight-lowering/anti-obesity medications within the past 90 days prior to enrollment in the study.
8. Current use of FDA-approved pharmacotherapy for AUD (acamprosate, disulfiram, naltrexone), or other medications that are used for AUD treatment including topiramate and bupropion. Due to the half-life of injectable naltrexone, we will exclude participants who have taken vivitrol in the past 30 days.
9. Current use of medications with known interactions with semaglutide
10. Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
11. Known history of alcoholic ketoacidosis, pancreatitis (either acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis
12. Known history of gastric bypass surgery
13. Known or suspected allergy to semaglutide, any of the product components, or any other GLP-1 analogue
14. Known history of suicidal attempts (within the past 24 months) or active suicidal ideation
15. Known history of vestibular disorders or clinically significant motion sickness
16. Known history of noise-induced hearing loss or tinnitus
17. Only for subjects undergoing brain scan: contraindication(s) for brain fMRI
18. Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)
19. 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 within the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable within the past twelve months.
20. Current stimulant or opioid use disorder.
21. Any other reason or clinical condition that the Investigators judge would interfere with study participation and/or be unsafe for a possible subject

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Katie Thompson, LMSW; ‪(405) 860-0069‬; kthom58@okstate.edu

Contact: William K Simmons, Ph.D.; kyle.simmons@okstate.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05891587
• Other Study ID Numbers: 202208
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD will be shared with other investigators upon reasonable request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Data will become available following publication of study manuscripts and will be available indefinitely.
• Access Criteria: Reasonable request from qualified investigator.

• Current Responsible Party: Oklahoma State University Center for Health Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Oklahoma State University Center for Health Sciences
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Drug Abuse

Investigators

• Principal Investigator: William K Simmons, Ph.D.; Oklahoma State University Center for Health Sciences

• PRS Account: Oklahoma State University Center for Health Sciences
• Verification Date: November 2023