Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence (COST)
|Cocaine Dependence||Drug: levodopa carbidopa and entacapone (LCE) Drug: Placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence|
- Cocaine Urine Toxicology [ Time Frame: collected 3x/week for 24 weeks of trial or for the duration of the participants involvement in the study. ]Abstinence will be assessed by urine toxicology results collected 3x/week during the 24 week trial or for the length of participation
- Retention in Treatment [ Time Frame: 12 weeks ]The number of participants who completed the 12-week medication phase of the study.
|Study Start Date:||July 2014|
|Study Completion Date:||December 2015|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
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
Placebo Comparator: Placebo
matched placebo for LCE condition dosed twice daily
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468012
|United States, New York|
|New York, New York, United States, 10032|
|Principal Investigator:||Adam Bisaga, M.D.||Columbia University|