The Effects of Exenatide, a GLP-1 Agonist, on Alcohol Self-Administration in Heavy Drinkers

January 14, 2022 updated by: Boston Medical Center
A double-blind, randomized, placebo-controlled, crossover design trial was used to test the effect of exenatide on alcohol self-administration and craving following a priming dose of alcohol. The specific objective of this research was to determine whether exenatide has effects on alcohol consumption.

Study Overview

Status

Terminated

Detailed Description

This proposal was intended to answer the call for accelerating drug development by exploring the potential of a glucagon-like peptide-1 (GLP-1) agonist, exenatide, as a candidate medication for the treatment of Alcohol Use Disorder. There is now substantial preclinical evidence that GLP-1 agonists can attenuate behaviors that model both the consumption and seeking of several commonly abused substances including alcohol, cocaine, and nicotine. This study was intended to accelerate medication development for Alcohol Use Disorder by testing a commercially-available and well-tolerated agent at a fraction of the cost of new drug discovery. None of the FDA-approved Alcohol Use Disorder medications or off-label Alcohol Use Disorder medications target this GLP-1 pathway, making exenatide a promising compound for Alcohol Use Disorder drug development.

The primary aim of this study was to test the effects of exenatide on alcohol self-administration and craving among heavy drinkers. In this within-subjects crossover design, 3 heavy drinkers were randomized to exposure order (exenatide or sham injection) prior to completing two alcohol self-administration trials. Subjects received a priming drink of alcohol and had access to 8 drinks over a 2-hour period. The investigators anticipated that subjects would consume less alcohol following the administration of exenatide compared to when they received a sham injection. Significant exenatide-induced reductions in drinking would be considered to be an indication that this drug may have value as an Alcohol Use Disorder medication. This study may provide a rationale for phase II randomized controlled trials testing exenatide with a treatment-seeking Alcohol Use Disorder population. These results may also help to spur further clinical investigation of the effects of exenatide and other available GLP-1 agonists on the factors implicated in the regulation of alcohol consumption.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University Psychiatry Research Center, Clinical Studies Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 21-55 years of age.
  2. Able to verify age with a state or federal picture identification.
  3. Exceeds safe weekly drinking limits [4 standard drink units (SDUs) for women or 21 SDUs for men per week]
  4. Reports at least one episode of binge drinking (>3 SDUs for women, >4 SDUs for men) an average of once per week in the four weeks prior to baseline screening.
  5. Meets Diagnostic And Statistical Manual Of Mental Disorders, Fifth Edition (DSM-5)criteria for mild alcohol use disorder or greater severity.

Exclusion Criteria:

  1. Seeking treatment for alcohol problems.
  2. Clinical Institute Withdrawal Assessment at ≥10
  3. DSM-5 diagnosis of current major depression, bipolar disorder, schizophrenia, bulimia/anorexia, dementia, or a substance use disorder other than alcohol, nicotine, marijuana or caffeine.
  4. If female, pregnant, nursing, have plans to become pregnant.
  5. If female, does not agree to use an accepted form of birth control.
  6. Has a medical contraindication to the use of exenatide.
  7. Has medical or mental condition for which further alcohol exposure at the planned dose range would be contraindicated.
  8. Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS).
  9. BMI is less than 18 or greater than or equal to 30.
  10. History of diabetes.
  11. Baseline hemoglobin A1c ≥ 6.5%
  12. Baseline non fasting glucose >200
  13. Significantly elevated serum lipase levels.
  14. Impaired renal function (GFR <80 mL/min).
  15. Pancreatitis, gastroparesis or other severe gastrointestinal disease.
  16. Has had gastric bypass surgery
  17. Subject is currently taking warfarin.
  18. Has received alcohol counseling or other non-pharmacologic intervention to treat AUD in the past 90 days.
  19. Has taken medications that are used to treat alcohol use disorder (AUD) in the past 90 days.
  20. Subjects with a history of thyroid cancer or other thyroid disease.
  21. Has urine toxicology results positive for cocaine, opioids, amphetamines, buprenorphine, methadone, or methamphetamines.
  22. Prior history of anaphylaxis or angioedema with another GLP-1 receptor agonist.
  23. Prior use of exenatide
  24. Liver function values AST or ALT are twice the normal limit
  25. Unable to comfortably abstain from nicotine for a period of 8 hours.
  26. Has Chronic obstructive pulmonary disease (COPD), history of solid organ transplant, sickle cell disease, severe heart disease or other health condition for which exposure to COVID-19 represents an unreasonable risk as determined by the study staff physician using accepted COVID-19 guidance (e.g. Centers for Disease Control, etc.).
  27. Subject has prior history of Drug-induced thrombocytopenia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exenatide then Placebo
This is a within subjects design study in which each subject receives both study drug and placebo. Subjects in this arm received a 5 mcg dose of immediate release exenatide on the day of the first alcohol self-administration trial. The 5mcg dose of exenatide was approved as the first dose administered to patients at the start of their treatment with this drug for FDA-approved indications. Subjects in this arm then received a sham injection on the day of the second alcohol self-administration trial. The sham injection was a needle stick using a syringe with no drug injected. Note that the volume of fluid injected for a 5mcg dose is so small that subjects would not sense this volume of fluid (or lack thereof) during the injection. Subjects were shielded from seeing the injection to maintain the blind.
Subject received an injection of 5 mcg of immediate release exenatide.
Other Names:
  • Byetta
Subjects received a sham injection with no study drug.
Other Names:
  • Placebo
Experimental: Placebo then Exenatide
This is a within subjects design study in which each subject receives both study drug and placebo. Subjects in this arm received a sham injection on the day of the first alcohol self-administration trial. The sham injection was a needle stick using a syringe with no drug injected. Subjects in this arm then received a 5 mcg dose of immediate release exenatide on the day of the second alcohol self-administration trial. The 5mcg dose of exenatide was approved as the first dose administered to patients at the start of their treatment with this drug for FDA-approved indications. Note that the volume of fluid injected for a 5mcg dose is so small that subjects would not sense this volume of fluid (or lack thereof) during the injection. Subjects were shielded from seeing the injection to maintain the blind.
Subject received an injection of 5 mcg of immediate release exenatide.
Other Names:
  • Byetta
Subjects received a sham injection with no study drug.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alcohol Consumption
Time Frame: 2 hours
Alcohol consumption was measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was not consumed. The amount not consumed was then subtracted from the total amount of alcohol served to the subject in order to calculate the amount consumed. This outcome was measured in standard drink units (SDUs). A standard drink contains approximately 0.6 fluid ounces of pure alcohol.
2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Eric Devine, PhD, Boston Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2019

Primary Completion (Actual)

July 1, 2021

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

August 21, 2018

First Submitted That Met QC Criteria

August 21, 2018

First Posted (Actual)

August 24, 2018

Study Record Updates

Last Update Posted (Actual)

February 9, 2022

Last Update Submitted That Met QC Criteria

January 14, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alcohol Use Disorder

Clinical Trials on Exenatide

Subscribe