Agonist Replacement Therapy for Cocaine Dependence

February 29, 2012 updated by: Craig Rush, University of Kentucky

Agonist Replacement Therapy for Cocaine Dependence: Identifying Novel Medications

Cocaine dependence is a significant public health concern. The proposed research will provide important clinical information regarding the efficacy of agonists replacement therapies for managing cocaine dependence.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cocaine abuse and dependence continue to be significant public health concerns. The number of Americans that used cocaine in the past month, the percentage of 12th-, 10th- and 8th-graders that used cocaine in the past year, and the percentage of treatment admissions involving cocaine has remained stable in recent years. In 1996, cocaine use cost society over $45 billion due to medical consequences, lost productivity and crime. Because of the public-health concerns and costs associated with its abuse, identifying a pharmacotherapy for cocaine dependence is a priority with the National Institute on Drug Abuse (N.I.D.A.). A pharmacological adjunct for cocaine dependence has not yet been identified.

The results of clinical trials suggest that agonist replacement therapies (e.g., d-amphetamine) may be effective for cocaine dependence. Because d-amphetamine reduces cocaine use, these clinical findings can be used as a reference to identify human laboratory procedures for screening putative pharmacotherapies. Identifying procedures for assessing the efficacy of putative pharmacotherapies is important because human laboratory studies can be conducted more rapidly and efficiently than clinical trials. The present project has two specific aims. The first specific aim is to demonstrate the sensitivity and predictive validity of human laboratory procedures commonly used to screen putative pharmacotherapies for cocaine dependence. To accomplish this aim, we will conduct two "proof-of-concept" studies. We will first demonstrate the safety and tolerability of d-amphetamine-cocaine combinations (Exp. 1). We will then demonstrate that d-amphetamine maintenance attenuates the reinforcing effects of cocaine (Exp. 2). The ability to attenuate the reinforcing effects of cocaine may be an important characteristic of an effective pharmacotherapy. The results of these studies will help elucidate the optimal conditions (e.g., dose) under which d-amphetamine might be expected to be effective. The second specific aim is to determine the efficacy of atomoxetine (Strattera®) as a putative agonist replacement pharmacotherapy for cocaine dependence. To accomplish this aim, we will conduct two experiments to determine the effects of cocaine during atomoxetine maintenance. We will first demonstrate the safety and tolerability of atomoxetine-cocaine combinations (Exp. 3). Finally, we will determine the reinforcing effects of intranasal cocaine during atomoxetine maintenance (Exp. 4). Atomoxetine, a potent norepinephrine uptake blocker, was chosen for study because its pharmacological and behavioral effects overlap to some extent with those of d-amphetamine, but it appears to have less abuse potential. Identifying novel agonist replacement therapies is important because clinicians may be reluctant to use d-amphetamine because of its abuse potential.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536 0086
        • University of Kentucky Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Must meet diagnostic criteria for cocaine dependence Current cocaine use at study entry, as determined by urine screen Body Mass Index less or equal to 30 ECG results within normal limits If female, willing to use contraception throughout study

Exclusion Criteria:

Meets diagnostic criteria for dependence on drug other than cocaine and nicotine Currently seeking treatment for substance abuse Current or past history of serious illness including impaired heart function, seizures and central nervous system tumors Family history o heart disease or seizures Current of past psychiatric disorder other than substance abuse Pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Drug: d-Amphetamine; Atomoxetine
Dexedrine (0-60 mg/day); Strattera (0-80 mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Behavioral effects of cocaine
Time Frame: Measure throughout the study
Measure throughout the study

Secondary Outcome Measures

Outcome Measure
Time Frame
Heart rate; blood pressure; ECG
Time Frame: Measure throughtout study
Measure throughtout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Kentucky

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Craig R Rush, Ph.D., University of Kentucky

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

June 11, 2008

First Submitted That Met QC Criteria

June 11, 2008

First Posted (Estimate)

June 13, 2008

Study Record Updates

Last Update Posted (Estimate)

March 1, 2012

Last Update Submitted That Met QC Criteria

February 29, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DA021155
  • DPMC (Other Identifier: NIDA)
  • Agonists for Cocaine Abuse
  • R01DA021155 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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