Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

NCT ID: NCT02080819

Last Updated: 2018-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2017-01-21

Brief Summary

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

Detailed Description

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).

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Healthy Control

Non drug using healthy controls

Group Type: NO_INTERVENTION

No interventions assigned to this group

Placebo

Placebo BID for 7 weeks

Group Type: PLACEBO_COMPARATOR

levodopa/carbidopa 400/100 BID

Intervention Type: DRUG

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.

Medication

Levodopa/carbidopa 400/100 BID for 7 weeks

Group Type: EXPERIMENTAL

levodopa/carbidopa 400/100 BID

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Sinemet; Parcopa

Eligibility Criteria

Inclusion Criteria

• Male and female subjects
• Age 18 to 50
• Meet current DSM-IV criteria for cocaine dependence who are seeking treatment.

Exclusion Criteria

1. Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, nicotine, or alcohol

2. Have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe

3. Significant current suicidal or homicidal ideation

4. 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)

5. Taking CNS active concomitant medications

6. 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)

7. Having conditions of probation or parole requiring reports of drug use to officers of the court

8. Impending incarceration

9. Pregnant or breast feeding for female patients

10. Inability to read, write, or speak English

11. Having plans to leave the immediate geographical area within 3 months

12. Unwillingness or not competent to sign a written informed consent form

13. Individuals who have pacemakers, metal or electromechanical implants or metallic foreign bodies

14. Patients who are known to be HIV positive will not be included due to possible CNS effects of HIV.

15. Alcohol withdrawal symptoms or history of significant previous alcohol withdrawal symptoms

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Liangsuo Ma, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1R01DA034131

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PT109865

Identifier Type: OTHER

Identifier Source: secondary_id

HM20000079

Identifier Type: -

Identifier Source: org_study_id