Efficacy of Levetiracetam in Cocaine-Abusing Methadone Maintained Patients
Condition: Cocaine Dependence; Opioid Dependency
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      Concurrent dependence on cocaine occurs in up to 50% of the over one million opiate dependent
      patients in spite of methadone maintenance treatment being highly effective for opiate
      dependence and having excellent treatment retention. Cocaine dependence has remained largely
      unresponsive to medications both in and outside of these methadone programs. We have initial
      data from our open-label study with levetiracetam showing that this medication is well
      tolerated and may reduce cocaine use in this cocaine-abusing methadone treated population.

      The specific aim of this study is to evaluate the efficacy of levetiracetam 3 grams/day in
      modifying cocaine-using behavior, reducing cocaine craving and attenuating cocaine's
      reinforcing effect among methadone-maintained patients. The primary outcomes will be
      reduction in cocaine use as assessed by self-report and thrice-weekly urinalyses. Secondary
      outcomes will include weeks in treatment (retention) and change in measures of cocaine
      craving, anxiety symptoms and opiate withdrawal symptoms.
    

Detailed description: 
      This 17-week double-blind, placebo controlled randomized pilot clinical trial will provide
      treatment for 40 cocaine-dependent opioid dependent patients. Participants, aged 18-65 years,
      will be randomized to receive levetiracetam 3000 mg/day or placebo while concurrently
      receiving treatment with methadone. Baseline cocaine use will be determined during the first
      week of treatment participation. (Gossop et al., 1997) The study design will have three
      overlapping phases that are summarized below: 1) A one week methadone fixed induction (week
      1) and flexible methadone stabilization phase (weeks 2-13); 2) an 12-week "treatment" phase
      (weeks 2-13), consisting of slow titration and stabilization on study medication; and 3) a
      four week "taper, detoxification or transfer" phase (weeks 13-17).

      During the first week of induction onto methadone, participants will be administered
      increasing doses of methadone starting at 30 mg daily and increased up to 60 mg daily by the
      end of the first week. This methadone dose will be adjusted for stabilization of opiate
      withdrawal symptoms using a flexible dosing from 40 mg up to 150 mg between weeks 2 to 12.
      This range has been found to be adequate for the vast majority of patients receiving
      methadone in our program and is designed to accommodate participants who may not be able to
      tolerate the higher maintenance doses or may still experience withdrawal symptoms,
      respectively. We may increase or decrease this amount on a case-by-case basis based on
      physician assessment of self-reported and observed symptoms.

      Starting on week 2 subjects will start study medication in one of two randomly assigned
      experimental groups: levetiracetam 3000 mg /day (active medication) or placebo (inactive
      medication). Concurrent with the stabilization on methadone, levetiracetam will be increased
      from 500mg/day on week 2 and this dose will be slowly titrated to a total of 3000mg/day or
      maximum tolerated dose (MTD). Subjects will remain on their full dosage through week 13.

      At the end of week 13, participants will undergo detoxification from methadone over a 4-week
      period (weeks 13-17) and discontinuation from levetiracetam over a concurrent 2-week period.

      All participants will receive weekly 1-hour of individual psychotherapy (Cognitive Behavioral
      Treatment) with experienced clinicians specifically trained to deliver the therapy and who
      will receive ongoing supervision. The primary outcomes will be reduction in cocaine use, as
      assessed by self-report and thrice-weekly urinalyses. Secondary outcomes will include weeks
      in treatment (retention), reported medication side effects (medication tolerability), and
      change in measures of: cocaine craving, anxiety symptoms and opiate withdrawal symptoms. This
      study will occur at the Outpatient Treatment Research Program in Building 36 at the VA CT
      Healthcare System.
    

Intervention name(s): levetiracetam; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The participants will start receiving Levetiracetam 500mg in the mornings of the first day on week 2. The dose will be titrated every third day, until the target dose of 3000mg/day is achieved by week 4. The study medication must be titrated to 3000 mg/day or to the subject's maximum tolerated dose (MTD). The physician overseeing this titration as well as all study staff will be blind to the subject's medication administration. The medication will be discontinued over a two-week period.
Intervention MeSH terms: Levetiracetam
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: GABAergic; levetiracetam