Semaglutide for Alcohol Use Disorder

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Pharmacotherapy development remains a critical objective for reducing health and societal burdens associated with alcohol use disorder (AUD). Developing targeted treatments for specific AUD subgroups is a key aim under the NIAAA medication development strategy. Among those with AUD, cigarette smokers comprise a sizable and critical subgroup with disproportionally high long-term health risks, making it a key priority to advance therapies for concurrent AUD and cigarette smoking. Recent preclinical evidence indicates that glucagon-type peptide-1, an incretin hormone, impacts both alcohol and nicotine motivation and intake. This project will utilize human laboratory screening procedures to evaluate a GLP-1 receptor agonist as a novel candidate therapy for smokers with AUD. Participants who meet criteria for AUD and report smoking will complete laboratory alcohol administration procedures while receiving medication or placebo. This study will provide initial human data on the effects of a GLP-1 receptor agonist in relation to alcohol-related outcomes, including both alcohol and nicotine motivation, in participants with AUD. Validation of a candidate monotherapy for joint alcohol and nicotine reduction could have substantial public health impact.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill

Criteria

Inclusion Criteria:

• Age 21-65

• Meeting DSM-5 criteria for current (past year) mild or moderate AUD (i.e., from 2-5 symptoms endorsed), and 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)

• Daily smoker, defined as reporting smoking 1+ cigarettes per day, on average, over the past 12 months (past year avg cigarettes per day ≥ 1) and daily/near-daily smoking in the past month (smoking at least 25 days in the past 30)

• 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:

• Regular use of electronic nicotine delivery systems (ENDs; vaping), cigars, chewing tobacco or snuff, based on at least weekly use in the past 30 days

• Past 30-day use of nicotine replacement therapies/products

• 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 or smoking cessation 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 TSH >6.0 mIU/L or <0.4 mIU/L 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) <25kg/m2 or >35kg/m2

• 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)