Imaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): levodopa carbidopa and entacapone (LCE); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 400mg/100mg/200mg, twice daily; matched placebo for LCE condition dosed twice daily
Intervention MeSH terms: Levodopa; Carbidopa; Entacapone; Carbidopa, levodopa drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cocaine dependence; levodopa; carbidopa; entacapone