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

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ClinicalTrials.gov Identifier: NCT03645408
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : May 21, 2019
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Boston Medical Center

Brief Summary:
A double-blind, randomized, placebo-controlled, crossover design trial will be 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 is 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 is 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 is 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 is to test the effects of exenatide on alcohol self-administration and craving among heavy drinkers. In this within-subjects crossover design, 36 heavy drinkers will be randomized to exposure order (exenatide or sham injection) prior to completing two alcohol self-administration trials. Subjects will receive a priming drink of alcohol and will have access to 8 drinks over a 2-hour period. The investigators anticipate that subjects will consume less alcohol following the administration of exenatide compared to when they receive a sham injection. Significant exenatide-induced reductions in drinking will 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a double-blind, randomized, placebo-controlled, crossover design trial that will test 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 will not be blinded to the study medication. These nurses' only role in the study will be providing injections of the study drug. All other staff will be blinded to medication assignments. The sham injection will be a needlestick using the exenatide multi-dose syringe with no drug injected. Note that the volume of fluid injected for a 5mcg dose is only .08ml. It is not expected that subjects will sense this volume of fluid (or lack thereof) during the injection. Subjects will be shielded from seeing the injection to maintain the blind. The individual who administers medication will 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
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol
Drug Information available for: Exenatide

Arm Intervention/treatment
Experimental: Exenatide injection
Subjects in this arm will receive a 5 mcg dose of immediate release exenatide on the day of the alcohol challenge. The 5mcg dose of exenatide is approved as the first dose to be administered to patients at the start of their treatment with this drug for FDA-approved indications.
Drug: Exenatide
5 mcg dose of immediate release exenatide
Other Name: byetta

Placebo Comparator: Placebo
Subjects in this arm will receive a sham injection on the day of the alcohol challenge. The sham injection will be 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 will sense this volume of fluid (or lack thereof) during the injection. Subjects will be shielded from seeing the injection to maintain the blind.
Other: Sham injection
Subjects will have a sham injection with no study drug
Other Name: Placebo




Primary Outcome Measures :
  1. Alcohol Consumption [ Time Frame: 4 hours ]
    Alcohol consumption will be measured by using a graduated cylinder to determine the amount of alcohol given to the subject that was not consumed. This outcome will be measured as standard drink units. A standard drink contains approximately 0.6 fluid ounces of pure alcohol.

  2. Alcohol Cravings [ Time Frame: 4 hours ]
    Alcohol craving will be measured by self report with the Visual Analog Scale . The Visual analog scale is a straight line with one end meaning no alcohol craving and the other end meaning intense alcohol craving. The Participant marks a point on the line that matches their amount of alcohol craving.


Secondary Outcome Measures :
  1. Blood Glucose [ Time Frame: 4 hours ]
    The proportion of subjects with blood glucose values below 50 mg/dl will be compared within subjects using the McNemar's test. We hypothesize that there will be no difference in blood glucose levels between the alcohol Challenge Trials.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 (14 drinks for women or 21 drinks for men per week)
  4. Reports at least one episode of binge drinking (>3 for women, >4 for men) an average of once per week in the four weeks prior to baseline screening.
  5. Meets Diagnostic Statistical Manual 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. Body Mass Index is less than 18 or greater than or equal to 30.
  10. History of diabetes.
  11. Baseline hemoglobin A1c ≥ 6.5%
  12. Baseline nonfasting 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 Alcohol use disorder in the past 90 days.
  19. Has taken medications that are used to treat Alcohol Use Disorder 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645408


Contacts
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Contact: Eric Devine, PhD 617-414-1990 eric.devine@bmc.org
Contact: Kathleen Reid, MA 617-414-1990 kathleen.reid@bmc.org

Locations
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United States, Massachusetts
Boston University Psychiatry Research Center, Clinical Studies Unit Recruiting
Boston, Massachusetts, United States, 02118
Contact: Eric G Devine, Ph.D.    617-414-1990    eric.devine@bmc.org   
Sponsors and Collaborators
Boston Medical Center
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
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Principal Investigator: Eric Devine, PhD Boston Medical Center

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Responsible Party: Boston Medical Center
ClinicalTrials.gov Identifier: NCT03645408     History of Changes
Other Study ID Numbers: H-38015
R21AA027332-01 ( U.S. NIH Grant/Contract )
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Alcoholism
Alcoholic Intoxication
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ethanol
Exenatide
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Hypoglycemic Agents
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists