Pramipexole as a Treatment for Cocaine Dependence

NCT ID: NCT01651377

Last Updated: 2014-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2012-12-31

Brief 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.

Detailed 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 It can therefore be safely used chronically at higher doses, whereas pergolide has been withdrawn from the market for causing cardiac valvulopathy.

Conditions

Cocaine Addiction; Cocaine Abuse; Cocaine Dependence; Substance Abuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive matching placebo pills. The placebo group is included to maintain the blind, rather than as a comparison group.

Pramipexole

Group Type: ACTIVE_COMPARATOR

Pramipexole

Intervention Type: DRUG

Participants will receive pramipexole ER 0.375, .075, 1.5, 2.25, and 3mg/d in an ascending-dose pattern.

Interventions

Pramipexole

Participants will receive pramipexole ER 0.375, .075, 1.5, 2.25, and 3mg/d in an ascending-dose pattern.

Intervention Type: DRUG

Placebo

Participants will receive matching placebo pills. The placebo group is included to maintain the blind, rather than as a comparison group.

Intervention Type: DRUG

Other Intervention Names

Mirapex; Sugar pill

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Thomas Newton

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Michael E. DeBakey VA Medical Center

Houston, Texas, United States

Countries

United States

References

Newton TF, Haile CN, Mahoney JJ 3rd, Shah R, Verrico CD, De La Garza R 2nd, Kosten TR. Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans. Psychiatry Res. 2015 Nov 30;230(1):44-9. doi: 10.1016/j.psychres.2015.07.073. Epub 2015 Jul 29.

Reference Type: DERIVED

PMID: 26239766 (View on PubMed)

Other Identifiers

5P50DA018197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DPMC

Identifier Type: OTHER

Identifier Source: secondary_id

H-28454

Identifier Type: -

Identifier Source: org_study_id