Cocaine Dependence
Conditions
Keywords
cocaine dependence
Brief summary
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.
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.
Interventions
BEHAVIORALCommunity 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.
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Binding Potential of [11C]Raclopride | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Craving, Withdrawal Symptoms, Pattern of Cocaine Use | 2x/week for 24 weeks | measurement of abstinence, measured as vouchers earned and clinical appointments attended using CRA |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cocaine Users Cocaine users receiving CRA | 25 |
| Control Subjects Healthy controls who undergo scans | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Control Subjects | Cocaine Users | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Continuous | 38 years STANDARD_DEVIATION 6 | 37 years STANDARD_DEVIATION 7 | 37 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 22 Participants | 22 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 25 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 |
Outcome results
Primary
Change From Baseline in the Binding Potential of [11C]Raclopride
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.
Time frame: baseline and 3 months
Population: Analysis for change in binding potential (binding potential difference; at baseline versus stimulant induced binding potential) was done with 24 cocaine users since one of the subjects only underwent baseline scanning. However, treatment data for all 25 cocaine users was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cocaine Users | Change From Baseline in the Binding Potential of [11C]Raclopride | -13.7 ratio | Standard Deviation 8.7 |
| Control Subjects | Change From Baseline in the Binding Potential of [11C]Raclopride | -5.8 ratio | Standard Deviation 8.6 |
p-value: 0.003ANOVA
Secondary
Cocaine Craving, Withdrawal Symptoms, Pattern of Cocaine Use
measurement of abstinence, measured as vouchers earned and clinical appointments attended using CRA
Time frame: 2x/week for 24 weeks
Population: The number of subjects was determined from previous studies using CM/CRA
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cocaine Users | Cocaine Craving, Withdrawal Symptoms, Pattern of Cocaine Use | 650 dollars | Standard Deviation 0.2 |
Comparison: The limbic striatum was our primary region of interest using an unpaired t test to compare BPND and deltaBPND between the treatment responders and non-responders.p-value: 0.001t-test, 2 sided