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

• Sponsor: Boston Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03645408
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 26
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Exenatide; Other: Sham injection	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention 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.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: Quadruple (Participant, Care Provider, Investigator, Outcomes 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.
• Primary Purpose: Treatment
• Official Title: The Effects of Exenatide, a GLP-1 Agonist, on Alcohol Self-Administration in Heavy Drinkers
• Actual Study Start Date: May 2, 2019
• Actual Primary Completion Date: Jul 1, 2021
• Actual Study Completion Date: Jul 1, 2021

Arms and Interventions

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.	Drug: Exenatide; Subject received an injection of 5 mcg of immediate release exenatide.; Other Names: Byetta ; Other: Sham injection; 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.	Drug: Exenatide; Subject received an injection of 5 mcg of immediate release exenatide.; Other Names: Byetta ; Other: Sham injection; Subjects received a sham injection with no study drug.; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Alcohol Consumption [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston University Psychiatry Research Center, Clinical Studies Unit	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston Medical Center
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 5, 2020
• Informed Consent Form - Oct 14, 2020

More Information

Publications

None provided.

• Responsible Party: Boston Medical Center
• ClinicalTrials.gov Identifier: NCT03645408
• Other Study ID Numbers: H-38015; R21AA027332-01
• First Posted: Aug 24, 2018
• Last Update Posted: Feb 9, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Boston Medical Center: exenatide; alcohol craving; alcohol consumption
• Additional relevant MeSH terms: Alcoholism; Alcoholic Intoxication; Exenatide

Study Results

Participant Flow

Pre-assignment Detail	8 subjects were consented, 3 subjects were randomized, and 3 subjects completed the study.

Arm/Group Title	Exenatide Then Placebo	Placebo Then Exenatide
Arm/Group 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. Sham injection: Subjects will have a sham injection with no study drug	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.
Period Title: Overall Study
STARTED	1	2
COMPLETED	1	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Exenatide Then Placebo	Placebo Then Exenatide	Total
Arm/Group 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. Exenatide: Subject received an injection of 5 mcg of immediate release exenatide. Sham injection: Subjects received a sham injection with no study drug.	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. Exenatide: Subject received an injection of 5 mcg of immediate release exenatide. Sham injection: Subjects received a sham injection with no study drug.	Total of all reporting groups
Overall Participants	1	2	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (0)	23.5 (2.12)	30.7 (12.5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	2 100%	3 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	2 100%	3 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 100%	0 0%	1 33.3%
White	0 0%	2 100%	2 66.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	2 100%	3 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide Injection	Sham Injection (Placebo)
Arm/Group Description	Subjects received a 5 mcg dose of immediate-release exenatide on the day of the alcohol self-administration trial. This is a within subjects design study in which each subject received both study drug and sham injection (placebo). 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.	Subjects received a sham injection on the day of the alcohol self-administration trial. This is a within subjects design study in which each subject received both study drug and sham injection (placebo). 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.
Measure Participants	3	3
Mean (Standard Deviation) [standard drink units (SDUs)]	0.93 (0.87)	2.78 (2.66)

Adverse Events

Time Frame	Up to 38 days
Adverse Event Reporting Description	The primary risks of this study were risks related to taking study medication, loss of confidentiality, discomfort with study procedures, overconsumption of alcohol, and interference with efforts for recovery from alcohol use disorder. The protocol was designed to minimize risk to subjects.
Arm/Group Title	Exenatide		Sham Injection (Placebo)
Arm/Group Description	Subjects received a 5 mcg dose of immediate-release exenatide on the day of the alcohol self-administration trial. This is a within subjects design study in which each subject received both study drug and sham injection (placebo). 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.		Subjects received a sham injection on the day of the alcohol self-administration trial. This is a within subjects design study in which each subject received both study drug and sham injection (placebo). 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.
All Cause Mortality
	Exenatide		Sham Injection (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Serious Adverse Events
	Exenatide		Sham Injection (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide		Sham Injection (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/3 (33.3%)
General disorders
Pre-drug injection anxiety	0/3 (0%)	0	1/3 (33.3%)	1
Nausea	1/3 (33.3%)	1	0/3 (0%)	0

Limitations/Caveats

The small sample size reflects the early termination of the research which was halted due to Covid 19 precautions.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.