Imaging the Neurobiology of a Behavioral Treatment for Cocaine Dependence (PET-CRA)

May 24, 2016 updated by: New York State Psychiatric Institute
The purpose of this study is to determine whether patients with the greatest loss of dopamine transmission due to cocaine dependence at pre-treatment PET and MRI scans will be those who fail to respond to substance abuse treatment. This study will also determine whether patients who do respond to treatment will experience a recovery of dopamine function. This study includes free brain imaging and behavioral intervention. Compensation provided for the brain scans.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Previous studies have shown that cocaine dependence is associated with a decrease in dopamine release in response to a psychostimulant challenge. We have recently completed a study demonstrating that this loss of pre-synaptic dopamine function is associated with the choice to self-administer cocaine in the presence of an alternative reinforcer. This finding consistent with animal models of reinforcement and which show that dopamine transmission serves to modulate reward based behavior, and in this case, allows for a more adaptive response to be made in the presence of a competing reinforcer.

The previous study was performed in non-treatment seeking cocaine dependent subjects using an inpatient laboratory model to measure the choice for cocaine. Thus, the goal of the present proposal is to investigate this association in a more realistic setting where cocaine dependent out patients face the choice between using cocaine and the alternative reinforcers presented to them in a therapeutic setting. The Community Reinforcement Approach with voucher incentives is a treatment for cocaine dependence that has been shown success in a number of controlled studies. Since the basis of this therapy is to reduce the reinforcing value of cocaine by increasing the density of alternative, healthy reinforcers, we have chosen to correlate outcome from this treatment with measures of presynaptic dopamine function. We propose to scan cocaine dependent patients with [11C]raclopride and oral methylphenidate in order to measure dopamine release. Patients will be scanned before treatment and at 12 weeks into therapy. We predict that the patients with the greatest loss of dopamine transmission at the pre-treatment scan will be those who fail to respond to treatment. Furthermore, we hypothesize that the patients who do respond to treatment will experience a recovery of dopamine function, measured at the post-treatment scan.

In addition, subjects enrolled in this study will undergo functional Magnetic Resonance Imaging (fMRI) and spectroscopy studies in order to asses differences in neuronal integrity, learning, and impulse control.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

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
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

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

21 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females between 21 and 45 years old
  • Fulfill DSMIV criteria for cocaine abuse or dependence
  • Able to give informed consent and comply with study procedures
  • Medically Healthy

Exclusion Criteria:

  • Major DSM-IV Axis I disorder other than cocaine abuse or dependence. Subjects with a history of other psychostimulant abuse/dependence or compulsive gambling will be excluded.
  • Current use of opiates, sedative-hypnotic, and/or cannabis more than twice a week (use less than twice a week is acceptable).
  • Current use of psychotropic medication such as antipsychotics or antidepressants.
  • Presence or positive history of severe medical or neurological illness (including epilepsy), or any cardiovascular disease, low hemoglobin (Hb < 14 gm/dL in males, Hb < 12 gm/dL in females), or SGOT or SGPT > 2-3 times normal. Chronic active hepatitis B or C will also be an exclusion criteria.
  • Resting SBP >150, DBP > 90
  • Pregnancy or lactation, lack of effective birth control during 15 days before the scans*
  • Evidence /report of any heart abnormality during intake medical history, EKG or physical exam.
  • Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock, PhD, Lippincott Williams and Wilkins, NY 2001.
  • Lifetime exposure to radiation in the workplace, or history of participation in nuclear medicine procedures, including research protocols **
  • Positive Allen Test indicating lack of collateral blood flow to hand
  • History of sensitivity to methylphenidate

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: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Contingency Management w/ CRA
Cocaine users: Contingency management w/ Community Reinforcement Approach
Behavioral: Community Reinforcement Approach
Community Reinforcement Approach (CRA): The community reinforcement treatment program will be carried out in accordance with NIDA's therapy manual (13).During weeks 13 through 24, patients will meet once per week with their therapists. Sessions will focus on promoting continued change in the life areas addressed in the first 12 weeks of treatment or new components are added as needed.
NO_INTERVENTION: Healthy Control
A group of healthy matched comparison subjects with no DSM-IV axis I Disorder was included; they were matched for cigarette smoking, gender, and ethnicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in the Binding Potential of [11C]Raclopride
Time Frame: baseline and 3 months
The relationship between Methylphenidate-induced Dopamine Release in the Striatum (Measured by Displacement of [11C]-Raclopride by Oral Methylphenidate) and Treatment Response (Measured Using Community Reinforcement Approach and Contingency Management) was studied. Dopamine Function was assessed by evaluation of endogenous Dopamine release over the course of treatment (i.e., at 3 months as compared to baseline). Endogenous Dopamine release is inversely related to the change in binding potential (delta BPND) of [11C]raclopride, in that a negative delta BPND, or increased displacement of [11C]raclopride, reflects an increase in the release of endogenous dopamine over the course of treatment.
baseline and 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cocaine Craving, Withdrawal Symptoms, Pattern of Cocaine Use
Time Frame: 2x/week for 24 weeks
measurement of abstinence, measured as vouchers earned and clinical appointments attended using CRA
2x/week for 24 weeks

Collaborators and Investigators

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

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Diana Martinez, MD, Research Foundation for Mental Hygiene, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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

July 1, 2006

Primary Completion (ACTUAL)

July 1, 2010

Study Completion (ACTUAL)

January 1, 2011

Study Registration Dates

First Submitted

September 14, 2006

First Submitted That Met QC Criteria

September 14, 2006

First Posted (ESTIMATE)

September 15, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

July 1, 2016

Last Update Submitted That Met QC Criteria

May 24, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #5158
  • R01DA020855-02 (NIH)

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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