Semaglutide for Alcohol Use Disorder

• ClinicalTrials.gov Identifier: NCT05520775
• Recruitment Status: Completed
• First Posted: August 30, 2022
• Last Update Posted: May 8, 2024
• Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Tracking Information

• First Submitted Date: August 26, 2022
• First Posted Date: August 30, 2022
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: September 2, 2022
• Actual Primary Completion Date: April 12, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2022)

• Change in Volume of Alcohol Consumed [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  Volume of alcohol consumed during a self-administration procedure
• Change in Breath Alcohol Concentration [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  Peak breath alcohol concentration during a self-administration procedure

Original Primary Outcome Measures (submitted: August 26, 2022)

• Volume of alcohol consumed [ Time Frame: Change in outcome from baseline (Week 0) to post-medication (Week 8) ]
  Volume of alcohol consumed during a self-administration procedure
• Breath alcohol concentration [ Time Frame: Change in outcome from baseline (Week 0) to post-medication (Week 8) ]
  Peak breath alcohol concentration during a self-administration procedure

Current Secondary Outcome Measures (submitted: September 1, 2022)

• Change in Subjective Stimulation from Alcohol (Biphasic Effects of Alcohol questionnaire) [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  Seven questions from the Biphasic Effects of Alcohol questionnaire used to collect self-reported feelings of stimulation during an alcohol challenge procedure. Possible responses are 0-10, 0 being "not at all" and 10 being "extremely". Scores range from 0 to 70. Higher scores indicate more stimulation effects.
• Change in Subjective Sedation from Alcohol (Biphasic Effects of Alcohol questionnaire) [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  Seven questions from the Biphasic Effects of Alcohol questionnaire used to collect self-reported sedative feelings during an alcohol challenge procedure. Possible responses are 0 "not at all" through 10 "extremely". Scores range from 0 to 70. Higher scores indicate more sedative effects.
• Change in Alcohol Demand (Alcohol Purchase Task) [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  The Alcohol Purchase Task is a 20-question self-reported measure to understand motivation for obtaining alcohol which asks participants about the number of drinks they would purchase and consume based on an increasing drink cost.
• Change in Cigarette Demand (Cigarette Purchase Task) [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  Self-reported cigarette demand during an alcohol challenge procedure
• Change in Daily Alcohol Use (Timeline Followback questionnaire) [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ]
  Self-reported drinks per day
• Change in Daily Cigarette Use (Timeline Followback questionnaire) [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ]
  Self-reported cigarettes per day

Original Secondary Outcome Measures (submitted: August 26, 2022)

• Subjective response to alcohol [ Time Frame: Change in outcome from baseline (Week 0) to post-medication (Week 8) ]
  Self-reported stimulation and sedation during an alcohol challenge procedure
• Drug demand [ Time Frame: Change in outcome from baseline (Week 0) to post-medication (Week 8) ]
  Self-reported alcohol and cigarette demand during an alcohol challenge procedure
• Daily alcohol use [ Time Frame: Change in outcome from baseline (Week 0) to study endpoint (Week 10) ]
  Self-reported drinks per day
• Daily cigarette use [ Time Frame: Change in outcome from baseline (Week 0) to study endpoint (Week 10) ]
  Self-reported cigarettes per day

Current Other Pre-specified Outcome Measures (submitted: September 1, 2022)

• Change in Weight [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ]
  Body weight
• Change in HbA1c [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ]
  Hemoglobin A1C (HbA1c)
• Change in Alcohol elimination [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
  Rate of alcohol elimination following an alcohol challenge procedure

Original Other Pre-specified Outcome Measures (submitted: August 26, 2022)

• Weight [ Time Frame: Change in outcome from baseline (Week 0) to study endpoint (Week 10) ]
  Body weight
• HbA1c [ Time Frame: Change in outcome from baseline (Week 0) to study endpoint (Week 10) ]
  Hemoglobin A1C
• Alcohol elimination [ Time Frame: Change in outcome from baseline (Week 0) to post-medication (Week 8) ]
  Rate of alcohol elimination following an alcohol challenge procedure

Descriptive Information

• Brief Title: Semaglutide for Alcohol Use Disorder
• Official Title: Human Laboratory Screening of Semaglutide for Alcohol Use Disorder
• Brief Summary: This is an early-Phase II human laboratory trial using a randomized, placebo-controlled, dose-ranging design to investigate the effects of semaglutide, a GLP-1 receptor agonist, on alcohol-related outcomes in adults with alcohol use disorder (AUD).
• Detailed Description: This is an early-Phase II human laboratory trial using a randomized, placebo-controlled, dose-ranging design to investigate the effects of semaglutide, a GLP-1 receptor agonist, on laboratory alcohol responses and consumption, naturalistic alcohol consumption, and weight loss in participants with alcohol use disorder (AUD). Participants will attend weekly visits while semaglutide dosage is increased to 1.0mg over a period of approximately 9-10 weeks. Participants will attend weekly visits for medication or placebo administration. At scheduled intervals, participants will complete 4 laboratory sessions involving alcohol self-administration and alcohol challenge to characterize medication effects on alcohol-related outcomes.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

Randomized parallel group design.

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

Condition

• Alcohol Use Disorder
• Cigarette Smoking

Intervention

• Drug: Semaglutide
  Semaglutide (subcutaneous)
• Drug: Sham/placebo
  Sham subcutaneous injection

Study Arms

• Experimental: Semaglutide
  Participants will receive semaglutide via subcutaneous injections at escalating doses (.25mg to 1.0mg) over 9 weeks.
  Intervention: Drug: Semaglutide
• Sham Comparator: Sham/Placebo
  Participants will receive sham subcutaneous injections over 9 weeks.
  Intervention: Drug: Sham/placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 26, 2022): 48
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 19, 2024
• Actual Primary Completion Date: April 12, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 21-65
• Meeting DSM-5 criteria for current (past year) alcohol use disorder (with 2-7 symptoms endorsed) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for current at-risk drinking (i.e., >7/14 drinks in one week for women/men, with at least two episodes of 4+/5+ drinks in the past 30 days)
• Willingness/availability to take study medication and complete study procedures, including attending weekly visits for medication administration, side effect assessments, and glucose monitoring
• Willingness to complete laboratory sessions involving alcohol administration
• Ability to communicate and read in English

Exclusion Criteria:

• Reporting past 30-day use of illicit drugs other than cannabis at baseline, or having a positive toxicology screen for illicit drugs other than cannabis at baseline
• Meeting past-year criteria for a substance use disorder (with the exception of alcohol, tobacco or mild cannabis use disorder)
• Current engagement in alcohol treatments, or currently engaged in intentional efforts to quit alcohol use
• Past 30-day use of: Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide;, or weight control medications
• Prior use of semaglutide or other GLP-1 agonists
• Known or suspected hypersensitivity to study medication or related products
• Lifetime diagnosis of severe mental illness (including schizophrenia and bipolar disorder)
• History of suicide attempt, or recent (past 30 day) suicidal ideation, or psychiatric hospitalization in the last 6 months
• Current significant medical or neurological illness (based on self-report or medical record) including severe hepatic impairment or cirrhosis, impaired renal function (eGFR <50ml/min), acute or chronic pancreatitis, gastroparesis, gallbladder disease or cholelithiasis, other severe gastrointestinal disease, heart failure, coronary artery disease, stroke, seizure disorder, or other medical condition that poses a risk for the medication or alcohol administration components of the study (as determined by the MD)
• A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B
• Calcitonin greater than or equal to 50 ng/L
• Uncontrolled thyroid disease at screening
• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
• History of Type 1 or Type 2 diabetes, or HbA1c >6.5% measured at screening
• History of diabetic retinopathy, proliferative retinopathy, or maculopathy
• History of diabetic ketoacidosis
• History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)

• Currently nursing, pregnant, anticipating pregnancy in the next 6 months, or not using a highly effective contraceptive method as judged by the MD, and defined as:

  1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  3. intrauterine device
  4. intrauterine hormone-releasing system
  5. bilateral tubal occlusion
  6. vasectomized partner
  7. sexual abstinence
• Elevation of serum lipase, amylase, direct (conjugated) bilirubin, or alkaline phosphatase (ALP), ALT, or AST) more than 3X the upper limit of normal on baseline bloodwork
• Baseline body mass index (BMI) <23kg/m^2
• Uncontrolled hypertension or systolic BP >180 mmHg and/or diastolic BP >105 mmHg, averaged from three measurements
• Plans for travel outside of the local area in the upcoming 12 weeks that would interfere with lab visits during the study period (or other logistic factors that would make it difficult to commit to entire duration of study)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05520775
• Other Study ID Numbers: 21-1689; R21AA026931-02 ( U.S. NIH Grant/Contract )
• 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

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: University of North Carolina, Chapel Hill
• Original Responsible Party: Christian Hendershot, MS, PhD, University of North Carolina, Chapel Hill, Research Associate Professor
• Current Study Sponsor: University of North Carolina, Chapel Hill
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Christian Hendershot, Ph.D.; UNC-Chapel Hill

• PRS Account: University of North Carolina, Chapel Hill
• Verification Date: May 2024