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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

cocaine hydrochloride

exenatide

placebo

About this trial

This is an interventional other trial for Cocaine Dependence

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Connecticut Mental Health Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

acute pre-treatment with exenatide

sub-chronic (5 day) treatment with exenatide

acute pre-treatment with placebo

sub-chronic (5 day) treatment with placebo

Arm Description

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

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).

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

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02302976

First Posted

November 24, 2014

Last Updated

February 14, 2023

Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT02302976

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

November 2014 (undefined)

Primary Completion Date

August 1, 2018 (Actual)

Study Completion Date

August 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cocaine Dependence

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

acute pre-treatment with exenatide

Arm Type

Experimental

Arm Description

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

Arm Title

sub-chronic (5 day) treatment with exenatide

Arm Type

Experimental

Arm Description

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).

Arm Title

acute pre-treatment with placebo

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

sub-chronic (5 day) treatment with placebo

Arm Type

Placebo Comparator

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

cocaine hydrochloride

Intervention Type

Drug

Intervention Name(s)

exenatide

Other Intervention Name(s)

byetta

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

Mean cocaine inter-infusion interval

Description

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.

Time Frame

3 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gustavo Angarita, M.D.

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Connecticut Mental Health Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

Cocaine Dependence

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial