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Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse

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ClinicalTrials.gov Identifier: NCT02080819
Recruitment Status : Completed
First Posted : March 6, 2014
Results First Posted : April 12, 2018
Last Update Posted : April 12, 2018
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Virginia Commonwealth University

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

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

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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 131 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Striatal Effective Connectivity to Predict Treatment Response in Cocaine Misuse
Study Start Date : February 2014
Actual Primary Completion Date : January 21, 2017
Actual Study Completion Date : January 21, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Healthy Control
Non drug using healthy controls
Placebo Comparator: Placebo
Placebo 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

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




Primary Outcome Measures :
  1. Cocaine Treatment Outcome [ Time Frame: Baseline to 12 weeks ]
    Treatment effectiveness score based on number of positive urine drug screens



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02080819


Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Liangsuo Ma, Ph.D. Virginia Commonwealth University
  Study Documents (Full-Text)

Documents provided by Virginia Commonwealth University:
Study Protocol  [PDF] October 1, 2013
Statistical Analysis Plan  [PDF] October 1, 2013


Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02080819     History of Changes
Other Study ID Numbers: HM20000079
1R01DA034131 ( U.S. NIH Grant/Contract )
PT109865 ( Other Identifier: Virginia Commonwealth University )
First Posted: March 6, 2014    Key Record Dates
Results First Posted: April 12, 2018
Last Update Posted: April 12, 2018
Last Verified: March 2018

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

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cocaine
Levodopa
Carbidopa
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors