Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

Study Overview
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Brief Summary
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This project proposes to investigate the role of brain connectivity in the mechanism of treatment response to dopaminergic medications in cocaine dependence.

Detailed Description
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This project will use stochastic DCM, which is a recent DCM extension that takes into account hidden fluctuations in neuronal and vascular responses, and thus is especially suited for investigating effects of disease or drugs. In addition, this project will use nonlinear DCM, a DCM extension that can measure gating effects by striatum on cortico-cortical pathways. The overall aims of this project are: (1) To conduct functional magnetic resonance imaging-based DCM studies of working memory and impulsivity in order to determine the effective (directional) connectivity between PFC and striatum in treatment-seeking Cocaine Dependent (CD) subjects compared to non-drug using controls. We hypothesize that DLPFC causally affects ventral striatum in CDs, and that the strength of this connection is lower in CDs compared to controls. (2) To determine whether the pretreatment gating effect by the dorsal striatum, as a reflection of pretreatment hypodopaminergic state associated with chronic compulsive drug use, predicts the treatment response to dopaminergic pharmacotherapy in CDs. We hypothesize that lower pretreatment gating by the dorsal striatum on prefrontal-parietal effective connectivity predicts greater 8-week improvement from treatment of CDs with DA enhancing medications (combined with cognitive behavioral therapy [CBT]), but not from treatment with placebo (combined with CBT).

Official Title
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Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

Conditions
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Cocaine Dependence

Intervention / Treatment
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* Drug: levodopa/carbidopa 400/100 BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects Age 18 to 50 Meet current DSM-IV criteria for cocaine dependence who are seeking treatment. Exclusion Criteria: Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, nicotine, or alcohol Have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe Significant current suicidal or homicidal ideation Medical conditions contraindicating levodopa/carbidopa or pharmacotherapy (e.g., evidence of any movement disorder, clinically significant pulmonary disease, cardiovascular disease, liver or kidney disease, seizure disorder) Taking CNS active concomitant medications Taking medications known to have significant drug interactions with the study medication (e.g., CYP P-450-2D6 inhibitors, such as tamoxifen, iron salts, pyridoxine, monoamine oxidase inhibitors, phenothiazines, selegiline, anesthetics) Having conditions of probation or parole requiring reports of drug use to officers of the court Impending incarceration Pregnant or breast feeding for female patients Inability to read, write, or speak English Having plans to leave the immediate geographical area within 3 months Unwillingness or not competent to sign a written informed consent form Individuals who have pacemakers, metal or electromechanical implants or metallic foreign bodies Patients who are known to be HIV positive will not be included due to possible CNS effects of HIV. Alcohol withdrawal symptoms or history of significant previous alcohol withdrawal symptoms

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy Control<br>Non drug using healthy controls | |
| Placebo Comparator: Placebo<br>Placebo BID for 7 weeks | Drug: levodopa/carbidopa 400/100 BID<br>* Levodopa dose escalation (1 week): Days 1-2, one 50/12.5 mg tablet BID; Days 3-4, one 100/25 mg tablet BID; Days 5-6, one 200/50 mg tablet BID; Day 7, one 400/100 mg tablet BID. Maintenance phase (7 weeks): One 400/100 mg Levodopa/Carbidopa tablet BID or placebo in conjunction with once weekly individual cognitive behavioral therapy plus contingency management for attendance.<br>* Other names: Parcopa;|
| Experimental: Medication<br>Levodopa/carbidopa 400/100 BID for 7 weeks | Drug: levodopa/carbidopa 400/100 BID<br>* Levodopa dose escalation (1 week): Days 1-2, one 50/12.5 mg tablet BID; Days 3-4, one 100/25 mg tablet BID; Days 5-6, one 200/50 mg tablet BID; Day 7, one 400/100 mg tablet BID. Maintenance phase (7 weeks): One 400/100 mg Levodopa/Carbidopa tablet BID or placebo in conjunction with once weekly individual cognitive behavioral therapy plus contingency management for attendance.<br>* Other names: Parcopa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Treatment Outcome | Treatment effectiveness score based on number of positive urine drug screens | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug abuse, cocaine, impulsivity, dopamine