Pramipexole as a Treatment for Cocaine Dependence

Substance Abuse Clinical Trial

Official title:

Pramipexole as a Treatment for Cocaine Dependence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01651377
• Other study ID #: H-28454
• Secondary ID: 5P50DA018197DPMC
• Status: Completed
• Phase: Phase 1
• First received: February 20, 2012
• Last updated: July 18, 2014
• Start date: October 2011
• Est. completion date: December 2012

Study information

• Verified date: July 2014
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purposes of this study are as follows: 1. To assess the cardiovascular and subjective effects of cocaine during treatment with pramipexole and placebo. 2. To assess the reinforcing effects of cocaine, measured using choice procedures, during treatment with pramipexole and placebo.

Description:

In this protocol we propose to assess the impact of treatment with higher doses of the potent D2/3 agonist pramipexole, using the extended release preparation that has been shown to produce continuous DA receptor stimulation. Pramipexole is a non-ergot DA 3 receptor-preferring agonist. In contrast to pergolide, bromocriptine and cabergoline, it does not stimulate 5-HT2B receptors and therefore does not cause cardiac valvulopathy. It can therefore be safely used chronically at higher doses, whereas pergolide has been withdrawn from the market for causing cardiac valvulopathy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Be English-speaking volunteers who are not seeking treatment at the time of the study. We require proficiency in English to ensure good communication with staff.

• Be aged between 18 and 55 years.

• Meet DSM-IV TR criteria for cocaine dependence.

• Have a self-reported history of using cocaine by the IV or smoked route.

• Have vital signs as follows: supine blood pressure > 100/65 mm Hg, a seated blood pressure of > 90/60 mm Hg, and an orthostatic change < 20 mm Hg systolic or <10 mm Hg diastolic on standing. To ensure that subjects will not be at risk from cocaine, the resting pulse must be < 90 bpm and the blood pressure must be < 150 mmHg systolic and < 90 mmHg diastolic.

• Have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exceptions: (a) total bilirubin must be < 2x upper limit of normal and ALT, AST, and alkaline phosphatase <3× the upper limit of normal and (b) kidney function tests (creatinine and BUN) within normal limits.

• Have a baseline ECG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant arrhythmias.

• Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator.

Exclusion Criteria:

• Have any history or evidence suggestive of seizure disorder or brain injury.

• Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, or epileptic seizure.

• Have neurological or psychiatric disorders, such as: psychosis, bipolar illness or major depression as assessed by SCID; organic brain disease or dementia assessed by clinical interview; history of any psychiatric disorder that would require ongoing treatment or that would make study compliance difficult; and history of suicide attempts within the past year and/or current suicidal ideation/plan.

• Have evidence of clinically significant heart disease or hypertension, as determined by the PI.

• Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI.

• Have evidence of untreated or unstable medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease.

• Have HIV and are currently symptomatic or are taking antiretroviral medication.

• Be pregnant or nursing. Females must provide negative pregnancy urine tests upon hospital admission and at the end of study participation. Females must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, or condoms with spermicide).

• Have asthma or currently use theophylline or other sympathomimetics.

• Have any other illness, condition, or use of psychotropic medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Cocaine Abuse
• Cocaine Addiction
• Cocaine Dependence
• Cocaine-Related Disorders
• Substance Abuse

Intervention

Drug:
• Pramipexole
Participants will receive pramipexole ER 0.375, .075, 1.5, 2.25, and 3mg/d in an ascending-dose pattern.
• Placebo
Participants will receive matching placebo pills. The placebo group is included to maintain the blind, rather than as a comparison group.

Locations

Country	Name	City	State
United States	Michael E. DeBakey VA Medical Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor College of Medicine	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effects of pramipexole and cocaine on cardiovascular measures	Before and after each cocaine infusion, physiologic responses will be closely monitored using repeated HR, BP, and ECG readings. To evaluate safety, a DSMB will meet annually and following any serious AE to examine data as well as any new published information on pramipexole relevant to the project. The number of AEs (including arrhythmias and ECG changes), changes in BP and HR, and changes in mood and psychiatric symptoms (using the BSI, BDI, POMS, and BPRS) will also be assessed throughout the study.	16 days	Yes
Secondary	The effects of pramipexole and cocaine on subjective measures	The ability of pramipexole, as compared to placebo, to reduce cocaine-induced craving and to reduce reinforcing effects produced by cocaine will be measured by: 1. VAS, Adjective Scales, and MCQ; 2. Choices for cocaine vs. money in the self-administration assay.	16 days	No