Back to results

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

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:

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

Sites / Locations

Boston University Psychiatry Research Center, Clinical Studies Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

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

NCT ID

NCT03645408

First Posted

August 21, 2018

Last Updated

January 14, 2022

Sponsor

Boston Medical Center

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

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

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

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

Arm Title

Placebo then Exenatide

Arm Type

Experimental

Arm Description

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

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

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs