GLP-1 Agonism for Blocking Cocaine Euphoria and Self-Administration

Sponsor
Yale University (Other)
Overall Status
Completed
CT.gov ID
NCT02302976
Collaborator
National Institute on Drug Abuse (NIDA) (NIH)
13
1
4
45
0.3

Study Details

Study Description

Brief Summary

The investigators plan to explore the effects of acute pre-treatment with the glucagon like peptide-1 (GLP-1) agonist, exenatide versus placebo, on the subjective (e.g., euphoric) and behavioral effects (e.g., self-administration) of cocaine in experienced, non-treatment seeking users of the drug. Additionally, the investigators plan to explore the effects of sub-chronic (5-day) treatment with exenatide as compared to placebo on the subjective (e.g., euphoric) and behavioral (self-administration) effects of cocaine in experienced, non-treatment seeking users of the drug.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
13 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
GLP-1 Agonism for Blocking Cocaine Euphoria and Self-Administration
Study Start Date :
Nov 1, 2014
Actual Primary Completion Date :
Aug 1, 2018
Actual Study Completion Date :
Aug 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: acute pre-treatment with exenatide

This arm plans to explore the effects of acute pre-treatment with the glucagon like peptide-1 (GLP-1) agonist, exenatide vs. placebo, on the subjective (e.g., euphoric) and behavioral effects (e.g., self-administration) of cocaine in experienced, non-treatment seeking users of the drug. We propose to study 24 subjects in a within-subject (two-day, randomized, placebo-controlled) human laboratory study of self-regulated cocaine administration. We hypothesize that acute treatment with exenatide will reduce cocaine-induced euphoria and self-regulated cocaine administration as compared to placebo

Drug: cocaine hydrochloride

Drug: exenatide
Other Names:
  • byetta
  • Experimental: sub-chronic (5 day) treatment with exenatide

    This arm plans to explore the effects of sub-chronic (5-day) treatment with exenatide as compared to placebo on the subjective (e.g., euphoric) and behavioral (self-administration) effects of cocaine in experienced, non-treatment seeking users of the drug. Upon completion of arm 1, subjects may opt to be randomized to five days of treatment with either exenatide or placebo, followed by a one-day human laboratory study of self-regulated cocaine administration. We hypothesize that subjects treated with exenatide (up to N=12) will demonstrate decreased self-regulated cocaine administration as compared to subjects treated with placebo (up to N=12).

    Drug: cocaine hydrochloride

    Drug: exenatide
    Other Names:
  • byetta
  • Placebo Comparator: acute pre-treatment with placebo

    This arm plans to explore the effects of acute pre-treatment with the glucagon like peptide-1 (GLP-1) agonist, exenatide vs. placebo, on the subjective (e.g., euphoric) and behavioral effects (e.g., self-administration) of cocaine in experienced, non-treatment seeking users of the drug. We propose to study 24 subjects in a within-subject (two-day, randomized, placebo-controlled) human laboratory study of self-regulated cocaine administration. We hypothesize that acute treatment with exenatide will reduce cocaine-induced euphoria and self-regulated cocaine administration as compared to placebo

    Drug: cocaine hydrochloride

    Drug: placebo

    Placebo Comparator: sub-chronic (5 day) treatment with placebo

    This arm plans to explore the effects of sub-chronic (5-day) treatment with exenatide as compared to placebo on the subjective (e.g., euphoric) and behavioral (self-administration) effects of cocaine in experienced, non-treatment seeking users of the drug. Upon completion of arm 1, subjects may opt to be randomized to five days of treatment with either exenatide or placebo, followed by a one-day human laboratory study of self-regulated cocaine administration. We hypothesize that subjects treated with exenatide (up to N=12) will demonstrate decreased self-regulated cocaine administration as compared to subjects treated with placebo (up to N=12).

    Drug: cocaine hydrochloride

    Drug: placebo

    Outcome Measures

    Primary Outcome Measures

    1. Mean cocaine inter-infusion interval [3 hours]

      Subjects will complete a 90 minute long "binge" cocaine self administration session (16mg/70kg). Mean inter-infusion intervals (time between cocaine boluses) will then be averaged by adding all intervals within the session and dividing by 90. Intervals during which pump access is withheld (due to increase in vital signs) will be excluded. Data on cocaine self-administration (total number of responses, infusions, and III), subjective effects, and vital signs will be checked for normality prior to analysis using Kolmogorov-Smirnov statistics and normal probability plots. The significance level for all statistical tests will be set at p<.05.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. age 18 - 50 years,

    2. voluntary, written, informed consent,

    3. physically healthy by medical history, physical, neurological, ECG, and laboratory examinations,

    4. DSM-IV criteria for Cocaine Abuse (305.60) or Cocaine Dependence (304.20)

    5. recent street cocaine use in excess of amounts to be administered in the current study,

    6. intravenous and/or smoked (crack/ freebase) use,

    7. positive urine toxicology screen for cocaine,

    8. for females, non-lactating, no longer of child-bearing potential (or agree to practice effective contraception during the study), and a negative serum pregnancy (β-HCG) test.

    Exclusion Criteria:
    1. Other drug dependence (except nicotine) as determined by urine toxicology or interview

    2. < 1 year of cocaine dependence,

    3. a primary major DSM-IV psychiatric diagnosis (schizophrenia, bipolar disorder, etc.), unrelated to cocaine,

    4. a history of significant medical (cardiovascular) or neurological illness, ie prior myocardial infarction, current active symptoms of cardiovascular disease / angina, evidence of cocaine-related cardiovascular symptoms, prior arrhythmias or need for cardiovascular resuscitation, neurovascular events such as transient ischemic attacks, stroke, and/or seizures Parameters re: elevations in vital signs are now explicitly specified under "Safety features built into our one-day self-administration paradigm).

    5. current use of psychotropic and/or potentially psychoactive prescription medication,

    6. seeking treatment for drug abuse/dependence (for experimental cocaine component),

    7. physical or laboratory (β-HCG) evidence of pregnancy.

    8. current use of any medication (prescription or over-the-counter) determined to cause potential drug interactions by the study physicians.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Connecticut Mental Health Center New Haven Connecticut United States 06519

    Sponsors and Collaborators

    • Yale University
    • National Institute on Drug Abuse (NIDA)

    Investigators

    • Principal Investigator: Gustavo Angarita, M.D., Yale University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gustavo Angarita, Assistant Professor of Clinical Psychiatry, Yale University
    ClinicalTrials.gov Identifier:
    NCT02302976
    Other Study ID Numbers:
    • 1409014655
    • 1R21DA040914-01A1
    First Posted:
    Nov 27, 2014
    Last Update Posted:
    Feb 26, 2021
    Last Verified:
    Feb 1, 2021
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 26, 2021