Semaglutide for Alcohol Use Disorder

• ClinicalTrials.gov Identifier: NCT05520775
• Recruitment Status: Recruiting
• First Posted: August 30, 2022
• Last Update Posted: October 12, 2022
• 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

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Alcohol Use Disorder; Cigarette Smoking	Drug: Semaglutide; Drug: Sham/placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized parallel group design.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Human Laboratory Screening of Semaglutide for Alcohol Use Disorder
• Actual Study Start Date: September 2, 2022
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: October 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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
2. Change in Breath Alcohol Concentration [ Time Frame: baseline (Week 0) to post-medication (Week 8) ]
   Peak breath alcohol concentration during a self-administration procedure

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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
5. Change in Daily Alcohol Use (Timeline Followback questionnaire) [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ]
   Self-reported drinks per day
6. Change in Daily Cigarette Use (Timeline Followback questionnaire) [ Time Frame: baseline (Week 0) to study endpoint (Week 10) ]
   Self-reported cigarettes per day

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Contacts

Contact: Christian Hendershot, Ph.D.; (919) 962-5565; christian_hendershot@med.unc.edu

Contact: Margret Powell; margret_powell@med.unc.edu

Locations

United States, North Carolina

UNC-Chapel Hill; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Christian Hendershot, Ph.D. 919-962-5565 christian_hendershot@med.unc.edu

Sponsors and Collaborators

University of North Carolina, Chapel Hill

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

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

More Information

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT05520775
• Other Study ID Numbers: 21-1689; R21AA026931-02 ( U.S. NIH Grant/Contract )
• First Posted: August 30, 2022
• Last Update Posted: October 12, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD will be shared with other investigators upon reasonable request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alcoholism; Alcohol Drinking; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders