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

Primary Purpose

Alcohol Use Disorder

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Exenatide
Sham injection
Sponsored by
Boston Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Use Disorder focused on measuring exenatide, alcohol craving, alcohol consumption

Eligibility Criteria

21 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Boston University Psychiatry Research Center, Clinical Studies Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Exenatide then Placebo

Placebo then Exenatide

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Alcohol Consumption
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.

Secondary Outcome Measures

Full Information

First Posted
August 21, 2018
Last Updated
January 14, 2022
Sponsor
Boston Medical Center
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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1. Study Identification

Unique Protocol Identification Number
NCT03645408
Brief Title
The Effects of Exenatide, a GLP-1 Agonist, on Alcohol Self-Administration in Heavy Drinkers
Official Title
The Effects of Exenatide, a GLP-1 Agonist, on Alcohol Self-Administration in Heavy Drinkers
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Due to COVID-19 hospital-wide policies halting recruitment
Study Start Date
May 2, 2019 (Actual)
Primary Completion Date
July 1, 2021 (Actual)
Study Completion Date
July 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston Medical Center
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder
Keywords
exenatide, alcohol craving, alcohol consumption

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
This is a double-blind, randomized, placebo-controlled, crossover design trial that tested the effect of exenatide on alcohol self-administration and craving following a priming dose of alcohol.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Nursing staff at the general Clinical Research unit were not blinded to the study medication. These nurses' only role in the study was providing injections of the study drug. All other staff were blinded to medication assignments. The sham injection was a needlestick using the exenatide multi-dose syringe with no drug injected. Note that the volume of fluid injected for a 5mcg dose was only .08ml. It is not expected that subjects would sense this volume of fluid (or lack thereof) during the injection. Subjects were shielded from seeing the injection to maintain the blind. The individual who administered medication did not participate in subject evaluation to maintain the study blind.
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exenatide then Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo then Exenatide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Exenatide
Other Intervention Name(s)
Byetta
Intervention Description
Subject received an injection of 5 mcg of immediate release exenatide.
Intervention Type
Other
Intervention Name(s)
Sham injection
Other Intervention Name(s)
Placebo
Intervention Description
Subjects received a sham injection with no study drug.
Primary Outcome Measure Information:
Title
Alcohol Consumption
Description
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.
Time Frame
2 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 21-55 years of age. Able to verify age with a state or federal picture identification. Exceeds safe weekly drinking limits [4 standard drink units (SDUs) for women or 21 SDUs for men per week] 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. Meets Diagnostic And Statistical Manual Of Mental Disorders, Fifth Edition (DSM-5)criteria for mild alcohol use disorder or greater severity. Exclusion Criteria: Seeking treatment for alcohol problems. Clinical Institute Withdrawal Assessment at ≥10 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. If female, pregnant, nursing, have plans to become pregnant. If female, does not agree to use an accepted form of birth control. Has a medical contraindication to the use of exenatide. Has medical or mental condition for which further alcohol exposure at the planned dose range would be contraindicated. Current risk of suicidality (MINI suicidality score greater than 8 (low risk) or Yes to the ideation question #4 of the C-SSRS). BMI is less than 18 or greater than or equal to 30. History of diabetes. Baseline hemoglobin A1c ≥ 6.5% Baseline non fasting glucose >200 Significantly elevated serum lipase levels. Impaired renal function (GFR <80 mL/min). Pancreatitis, gastroparesis or other severe gastrointestinal disease. Has had gastric bypass surgery Subject is currently taking warfarin. Has received alcohol counseling or other non-pharmacologic intervention to treat AUD in the past 90 days. Has taken medications that are used to treat alcohol use disorder (AUD) in the past 90 days. Subjects with a history of thyroid cancer or other thyroid disease. Has urine toxicology results positive for cocaine, opioids, amphetamines, buprenorphine, methadone, or methamphetamines. Prior history of anaphylaxis or angioedema with another GLP-1 receptor agonist. Prior use of exenatide Liver function values AST or ALT are twice the normal limit Unable to comfortably abstain from nicotine for a period of 8 hours. 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.). Subject has prior history of Drug-induced thrombocytopenia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Devine, PhD
Organizational Affiliation
Boston Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boston University Psychiatry Research Center, Clinical Studies Unit
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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