Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence

NCT ID: NCT01468012

Last Updated: 2018-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-12-31

Brief Summary

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.

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.

Conditions

Cocaine Dependence

Study Design

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

Study Groups

levodopa carbidopa and entacapone (LCE)

400mg/100mg/200mg, twice daily dosing of levodopa carbidopa and entacapone (LCE)

Group Type: EXPERIMENTAL

levodopa carbidopa and entacapone (LCE)

Intervention Type: DRUG

400mg/100mg/200mg, twice daily

Placebo

placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

matched placebo for LCE condition dosed twice daily

Interventions

levodopa carbidopa and entacapone (LCE)

400mg/100mg/200mg, twice daily

Intervention Type: DRUG

Placebo

matched placebo for LCE condition dosed twice daily

Intervention Type: DRUG

Eligibility 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.

• 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

• 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.).

• 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.).

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Adam Bisaga

Research Psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adam Bisaga, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

STARS

New York, New York, United States

Countries

United States

Other Identifiers

6022

Identifier Type: OTHER

Identifier Source: secondary_id

#6022

Identifier Type: -

Identifier Source: org_study_id