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

NCT02302976 | Completed Phase 1 DMC

• 2 other identifiers: 14090146551R21DA040914-01A1
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Mean cocaine inter-infusion interval

  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.

  3 hours

Study Arms (4)

acute pre-treatment with exenatide

EXPERIMENTAL

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

sub-chronic (5 day) treatment with exenatide

EXPERIMENTAL

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

acute pre-treatment with placebo

PLACEBO COMPARATOR

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

sub-chronic (5 day) treatment with placebo

PLACEBO COMPARATOR

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

Interventions

cocaine hydrochloride DRUG

acute pre-treatment with exenatide; acute pre-treatment with placebo; sub-chronic (5 day) treatment with exenatide; sub-chronic (5 day) treatment with placebo

exenatide DRUG

Also known as: byetta

acute pre-treatment with exenatide; sub-chronic (5 day) treatment with exenatide

placebo DRUG

acute pre-treatment with placebo; sub-chronic (5 day) treatment with placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age 18 - 50 years,
• voluntary, written, informed consent,
• physically healthy by medical history, physical, neurological, ECG, and laboratory examinations,
• DSM-IV criteria for Cocaine Abuse (305.60) or Cocaine Dependence (304.20)
• recent street cocaine use in excess of amounts to be administered in the current study,
• intravenous and/or smoked (crack/ freebase) use,
• positive urine toxicology screen for cocaine,
• 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.

You may not qualify if:

• Other drug dependence (except nicotine) as determined by urine toxicology or interview
• \< 1 year of cocaine dependence,
• a primary major DSM-IV psychiatric diagnosis (schizophrenia, bipolar disorder, etc.), unrelated to cocaine,
• 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).
• current use of psychotropic and/or potentially psychoactive prescription medication,
• seeking treatment for drug abuse/dependence (for experimental cocaine component),
• physical or laboratory (β-HCG) evidence of pregnancy.
• current use of any medication (prescription or over-the-counter) determined to cause potential drug interactions by the study physicians.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Cocaine; Exenatide

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Gustavo Angarita, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: November 27, 2014
• Study Start: November 1, 2014
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

US (1)