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

Yale University

Status and phase: Completed; Phase 1

Conditions: Cocaine Dependence

Treatments: Drug: placebo; Drug: cocaine hydrochloride; Drug: exenatide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02302976

1409014655

1R21DA040914-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

13 participants in 4 patient groups, including a placebo group

acute pre-treatment with exenatide

Experimental group

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

Treatment:

Drug: cocaine hydrochloride

Drug: exenatide

sub-chronic (5 day) treatment with exenatide

Experimental group

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).

Treatment:

Drug: cocaine hydrochloride

Drug: exenatide

acute pre-treatment with placebo

Placebo Comparator group

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

Treatment:

Drug: cocaine hydrochloride

Drug: placebo

sub-chronic (5 day) treatment with placebo

Placebo Comparator group

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).

Treatment:

Drug: cocaine hydrochloride

Drug: placebo