Clinical trial NCT05520775: Semaglutide for Alcohol Use Disorder
Official title: Human Laboratory Screening of Semaglutide for Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Use Disorder
Cigarette Smoking
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2022-08-30
Enrollment: 48
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized parallel group design.
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Change in Alcohol Consumed
timeFrame: Baseline (Week 0) to post-medication (Week 8)
measure: Change in Breath Alcohol Concentration
timeFrame: Baseline (Week 0) to post-medication (Week 8)
Secondary outcomes:
measure: Change in Subjective Stimulation (Biphasic Alcohol Effects Scale)
timeFrame: Baseline (Week 0) to post-treatment (Week 8)
measure: Change in Subjective Sedation (Biphasic Alcohol Effects Scale)
timeFrame: baseline (Week 0) to post-medication (Week 8)
measure: Change in Alcohol Demand (Alcohol Purchase Task)
timeFrame: Baseline (Week 0) to post-treatment (Week 8)
measure: Change in Cigarette Demand (Cigarette Purchase Task)
timeFrame: Baseline (Week 0) to Post-medication (Week 8)
measure: Change in Daily Alcohol Use
timeFrame: baseline (Week 0) to study endpoint (Week 10)
measure: Change in Daily Cigarette Use
timeFrame: baseline (Week 0) to study endpoint (Week 10)
Other outcomes:
measure: Change in Weight
timeFrame: baseline (Week 0) to study endpoint (Week 10)
measure: Change in HbA1c
timeFrame: baseline (Week 0) to study endpoint (Week 10)
measure: Change in Alcohol Elimination
timeFrame: baseline (Week 0) to post-medication (Week 8)
Locations:
city: Chapel Hill
country: United States
facility: UNC-Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC-Chapel Hill
name: Christian Hendershot, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: