STAR-T: Semaglutide Therapy for Alcohol Reduction - Tulsa

Sponsor

Oklahoma State University Center for Health Sciences (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05891587

Collaborator

National Institute of Drug Abuse (U.S. Fed)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Semaglutide Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Semaglutide Therapy for Alcohol Reduction - Tulsa

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Semaglutide

Participants will receive subcutaneous injections of semaglutide in escalating doses (.25mg to 1.0mg) over the course of 12 weeks.

Drug: Semaglutide

Semaglutide pen injector

Placebo Comparator: Placebo

Participants will receive subcutaneous injections of a placebo saline solution over the course of 12 weeks.

Drug: Placebo

Saline solution

Outcome Measures

Primary Outcome Measures

Change in alcohol drinking [Baseline (Week 1) to post-medication (Week 13]
Difference in number of standard alcoholic drinks consumed/week (Drinks Per Week, DPW)

Secondary Outcome Measures

Change in heavy drinking days [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 [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) [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 [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 [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 [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 [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 [Baseline (Week 1) to post-medication (Week 13)]
Difference in activity of inhibitory brain regions during an alcohol-related Go/No-Go fNIRS task.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to provide informed consent before any trial-related activities
Male or female individuals who are at least 18 years old
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))
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 is ≤ 10
Able to speak, read, write, and understand English
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
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:

BMI < 25 kg/m2 or BMI ≥ 50 kg/m2
Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
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

Present diagnosis of diabetes or blood hemoglobin A1c (HbA1c) ≥ 6.5 %
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
Current or prior use of semaglutide (Ozempic or Wegovy) or tirzepatide (Mounjaro).
Use of weight-lowering/anti-obesity medications within the past 90 days prior to enrollment in the study.
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.
Current use of medications with known interactions with semaglutide
Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
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
Known history of gastric bypass surgery
Known or suspected allergy 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 vestibular disorders or clinically significant motion sickness
Known history of noise-induced hearing loss or tinnitus
Only for subjects undergoing brain scan: 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 within the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable within the past twelve months.
Current stimulant or opioid use disorder.
Any other reason or clinical condition that the Investigators judge would interfere with study participation and/or be unsafe for a possible subject