Pramipexole as a Treatment for Cocaine Dependence

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.

Study Overview

• Status: Completed
• Conditions: Substance Abuse; Cocaine Dependence; Cocaine Abuse; Cocaine Addiction
• Intervention / Treatment: Drug: Placebo; Drug: Pramipexole

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 It can therefore be safely used chronically at higher doses, whereas pergolide has been withdrawn from the market for causing cardiac valvulopathy.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Participants will receive matching placebo pills. The placebo group is included to maintain the blind, rather than as a comparison group.; Other Names: Sugar pill
Active Comparator: Pramipexole	Drug: Pramipexole; Participants will receive pramipexole ER 0.375, .075, 1.5, 2.25, and 3mg/d in an ascending-dose pattern.; Other Names: Mirapex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Institute on Drug Abuse (NIDA)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 20, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (Estimate): July 27, 2012

Study Record Updates

• Last Update Posted (Estimate): July 22, 2014
• Last Update Submitted That Met QC Criteria: July 18, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Cocaine; Pramipexole; Mirapex
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: H-28454; DPMC (Other Identifier: NIDA); 5P50DA018197 (U.S. NIH Grant/Contract)