The Effects of Exenatide, a GLP-1 Agonist, on Alcohol Self-Administration in Heavy Drinkers
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcoholic Intoxication
Intervention: Exenatide; Sham injection
Intervention description: Subject received an injection of 5 mcg of immediate release exenatide.; Subjects received a sham injection with no study drug.
Intervention MeSH terms: Exenatide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
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.
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.
Enrollment: 8.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: exenatide; alcohol craving; alcohol consumption

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.
    

Eligibility 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 [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