Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Virginia Commonwealth University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT02080819
First received: March 4, 2014
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Cocaine Dependence
Drug: levodopa/carbidopa 400/100 BID
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • 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


Estimated Enrollment: 90
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)
Arms Assigned Interventions
No Intervention: Healthy Control
Non drug using healthy controls
Placebo Comparator: Placebo
Experimental: Medication
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.

Other Names:
  • Sinemet
  • Parcopa

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).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02080819

Contacts
Contact: Lori Keyser-Marcus, Ph.D. 804-828-4164 lakeyser@vcu.edu

Locations
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Liangsuo Ma, Ph.D. Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02080819     History of Changes
Other Study ID Numbers: HM 20000079, 1R01DA034131, PT109865
Study First Received: March 4, 2014
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Virginia Commonwealth University:
drug abuse
cocaine
impulsivity
dopamine

Additional relevant MeSH terms:
Cocaine
Levodopa
Carbidopa
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Antiparkinson Agents
Anti-Dyskinesia Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014