Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence (COST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by New York State Psychiatric Institute
Sponsor:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01468012
First received: November 7, 2011
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The proposed study will look at cocaine dependent individuals and will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication of levodopa,carbidopa and entacapone (LCE) and will undergo brain imaging and 3) the 24 weeks outpatient treatment trial. The purpose is to see if treatment with LCE may reverse baseline brain deficits and if this change is associated with clinical improvement. Hypothesis is that treatment with LCE, compared to placebo, increases abstinence from cocaine over a 12-week trial in combination with behavioral treatment with voucher incentives.


Condition Intervention Phase
Cocaine Dependence
Drug: levodopa carbidopa and entacapone (LCE)
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Cocaine urine toxicology [ Time Frame: collected 3x/week for 24 weeks of trial or for the duration of the participants involvement in the study. ] [ Designated as safety issue: Yes ]
    Abstinence will be assessed by urine toxicology results collected 3x/week during the 24 week trial or for the length of participation


Estimated Enrollment: 100
Study Start Date: February 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: levodopa carbidopa and entacapone (LCE)
400mg/100mg/200mg, twice daily dosing of levodopa carbidopa and entacapone (LCE)
Drug: levodopa carbidopa and entacapone (LCE)
400mg/100mg/200mg, twice daily
Other Name: levodopa carbidopa and entacapone (LCE)
Placebo Comparator: Placebo
placebo
Drug: Placebo
matched placebo for LCE condition dosed twice daily
Other Name: Placebo

Detailed Description:

Cocaine dependence remains a serious public health problem; however no clearly effective pharmacological treatments have been identified to date. The investigators hypothesize that identification of subgroups of cocaine-dependent patients will help to develop targeted and more effective treatments. The investigators have observed that 30-40% of cocaine-dependent patients who enter our medication trials achieve abstinence during the lead-in period (the two weeks prior to starting medication). Initial abstinence is strongly predictive of abstinence during the subsequent medication trial. The investigators have also observed that a low dopamine release in the striatum is associated with greater choice of cocaine in volunteers and failure of cocaine-dependent patients to respond to behavioral treatment. The investigators hypothesize that individuals who have difficulties in achieving abstinence have a deficit in dopaminergic functioning and correcting this deficit using dopaminergic medication LCE (levodopa in combination with carbidopa and entacapone) will result in clinical improvement.

The proposed study will consist of three consecutive phases: 1) the 2-week outpatient lead-in phase during which behavioral therapy will be administered; 2) the 15-21 day inpatient phase (during which participants will start study medication and will undergo brain imaging; one PET and two fMRI scan sessions); and 3) the 24 weeks outpatient treatment trial.

Study medication (LCE or placebo) will be administered in a double-blind, placebo controlled manner for one week during inpatient phase followed by 12 weeks of the outpatient trial. During the remaining 12 weeks of the outpatient trial participants will receive therapy only.

The purpose of the lead-in phase is to identify patients who do not achieve abstinence in response to behavioral treatment. Subsequently, two matched subgroups of participants (half who achieved abstinence and half who did not achieve abstinence) will undergo the [11C] raclopride displacement PET brain imaging procedure. This procedure allows the measurement of dopamine release in response to a single dose of methylphenidate, and the investigators will determine if failure to achieve abstinence during the lead-in period is associated low dopamine transmission.

All participants in the proposed study will also undergo a functional MRI with the Motivational Incentive Delay task (fMRI/MID). This task is thought to reflect dopaminergic transmission in the brain-reward system but is safer and more feasible than PET. The investigators hypothesize that fMRI/MID will correlate strongly with results from the PET procedure, thereby suggesting that it also reflects the status of striatal dopamine functioning. In addition, a group of healthy controls will undergo one fMRI scan in order to validate the procedure and to assess if a deficit can be detected in cocaine-dependent participants. Cocaine-dependent participants will undergo two fMRI/MID, one at baseline and another after a week of treatment with LCE to assess if treatment with LCE may reverse baseline deficits and if this change is associated with clinical improvement.

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult, age 21-50.
  • Meets DSM-IV criteria for current cocaine dependence, supported by a positive urine for cocaine metabolites
  • Voluntarily seeking treatment for cocaine dependence
  • Absence of other medical or psychiatric disorders that are unstable and would interfere with participation.
  • Absence of any suspicious skin changes, suggestive of melanoma, during the full body exam
  • Able to give informed consent.

Exclusion Criteria:

  • Current DSM-IV criteria of other substance use disorders with the exception of nicotine dependence, and mild to moderate alcohol or cannabis abuse or dependence. Alcohol or cannabis abuse or dependence may be included provided that cocaine is the predominant problem, and medical detoxification is not indicated; alcohol and cannabis use are common among cocaine dependent patients and their categorical exclusion would impede recruitment and result in a sample of limited generalizability; secondary analyses will explore whether they exert any moderating effects on the main findings.
  • Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-IV organic mental disorder, psychotic disorder, bipolar disorder, recurrent severe MDD, OCD, or eating disorder. Participants with depressive disorder (provided that the score on the Hamilton Depression Scale is less than 20) and those with ADHD symptoms may be included, since these are common, often reflect effects of chronic drug use, and may improve with behavioral treatment and cessation or reduction of drug use.
  • Unstable medical disorders, or medical disorders that might interfere with study participation, including seizure disorder.
  • Significant current suicidal risk or 1 or more suicide attempts within the past year
  • Concurrent treatment with psychotropic medications
  • Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control
  • Baseline systolic BP of > 140 and < 100, diastolic BP > 90 and < 60 and baseline HR greater than 90.
  • Any clinically significant heart abnormality or cardiovascular disease
  • History of glaucoma
  • History of melanoma or current suspicious undiagnosed skin lesions
  • History of allergic reaction or adverse reaction to study medications (levodopa/carbidopa/entacapone; methylphenidate; raclopride).
  • Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" by Shellock
  • Lifetime exposure to radiation in the workplace, or history of participation in nuclear medicine procedures, including research protocols
  • Individuals who are predominantly left handed. Based on a score <50 on the Edinburg Handed Inventory (E.H.I.).

Inclusion Criteria(fMRI study-healthy controls):

  • Adult, age 21-50.
  • No current DSM-IV psychiatric or substance use disorders
  • Absence of other medical disorders that are unstable and would interfere with participation.
  • Able to give informed consent.

Exclusion Criteria (fMRI study-healthy controls):

  • Current or recent DSM-IV psychiatric or substance use disorders
  • Past history of any major Axis I disorder (e.g., psychotic disorders, bipolar disorder, recurrent major depressive disorder, OCD or eating disorders).
  • Unstable medical disorders, or medical disorders that might interfere with study participation.
  • Concurrent treatment with psychotropic medications
  • Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory method of birth control *
  • Baseline systolic BP of > 140 and < 100, diastolic BP > 90 and < 60 and baseline HR greater than 90.
  • Any clinically significant heart abnormality or cardiovascular disease
  • History of allergic reaction or adverse reaction to study medications (methylphenidate; raclopride).
  • Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" by Shellock
  • Individuals who are predominantly left handed. Based on a score <50 on the Edinburg Handed Inventory (E.H.I.).
  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: NCT01468012

Contacts
Contact: elizabeth Martinez 212- 923-3031 martine@nyspi.columbia.edu
Contact: daniel Brooks 212 923-3031 brooksd@nyspi.columbia.edu

Locations
United States, New York
STARS Recruiting
New York, New York, United States, 10032
Contact: Elizabeth Martinez    212-923-3031    martine@nyspi.columbia.edu   
Contact: daniel brooks    212-740-3205    brooksd@nyspi.columbia.edu   
Principal Investigator: Adam Bisaga, M.D.         
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Adam Bisaga, M.D. Columbia University
  More Information

No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01468012     History of Changes
Other Study ID Numbers: #6022, 6022
Study First Received: November 7, 2011
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:
cocaine dependence
levodopa
carbidopa
entacapone

Additional relevant MeSH terms:
Cocaine-Related Disorders
Substance-Related Disorders
Mental Disorders
Carbidopa
Levodopa
Carbidopa, levodopa drug combination
Entacapone
Cocaine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Dopamine Agonists
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on July 10, 2014