Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse
This project proposes to investigate the role of brain connectivity in the mechanism of treatment response to dopaminergic medications in cocaine dependence.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse|
- Cocaine treatment outcome [ Time Frame: last two weeks of treatment phase (weeks 8 & 9) ] [ Designated as safety issue: No ]The proportion of subjects in each treatment group who are cocaine abstinent during the last 2 weeks of treatment
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
No Intervention: Healthy Control
Non drug using healthy controls
|Placebo Comparator: Placebo|
Levodopa/carbidopa 400/100 BID for 7 weeks
Drug: levodopa/carbidopa 400/100 BID
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.
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02080819
|Contact: Lori Keyser-Marcus, Ph.D.||firstname.lastname@example.org|
|United States, Virginia|
|Virginia Commonwealth University||Recruiting|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Liangsuo Ma, Ph.D.||Virginia Commonwealth University|