Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

Cocaine Dependence Clinical Trial

Official title:

Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02080819
• Other study ID #: HM20000079
• Secondary ID: 1R01DA034131PT10
• Status: Completed
• Phase: Phase 2
• First received: March 4, 2014
• Last updated: March 16, 2018
• Start date: February 2014
• Est. completion date: January 21, 2017

Study information

• Verified date: March 2018
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: January 21, 2017
• Est. primary completion date: January 21, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders

Intervention

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.

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cocaine Treatment Outcome	Treatment effectiveness score based on number of positive urine drug screens	Baseline to 12 weeks