Levetiracetam (Keppra) Tolerability in Cocaine Abusing Methadone-maintained Patients.
Condition: Cocaine Dependence; Opioid Dependence
MeSH terms: Cocaine-Related Disorders; Opioid-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      The proposed investigation will use methadone maintained patients who have concurrent cocaine
      dependence in order to take advantage of the excellent (over 80%) treatment retention in this
      patient group and to maximize treatment compliance by daily observed medication with both
      methadone and levetiracetam. In the initial patients we will explore the tolerability of
      escalating doses of levetiracetam as well as its potential role in reducing cocaine use, as
      monitored by self-report and verified by three-times weekly urine toxicology testing in
      methadone treated patients.The specific aim of this study is to evaluate the tolerability and
      efficacy of levetiracetam 3 grams/day in modifying cocaine-using behavior, reducing cocaine
      craving and attenuating cocaine's reinforcing effect among methadone-maintained patients
    

Detailed description: 
      This 12-week open-label clinical trial will provide treatment for 15 cocaine-dependent opioid
      dependent patients. Participants, aged 18-65 years, will receive levetiracetam 3000 mg/day
      while concurrently receiving treatment with methadone. Baseline cocaine use will be
      determined during the first week of treatment participation.

      The study design will have three overlapping phases that are summarized below: 1) A one week
      methadone fixed induction (week 1) and flexible stabilization phase (weeks 2-9); 2) an 8-week
      "treatment" phase (weeks 2-9), consisting of slow titration and stabilization on study
      medication; and 3) a four week "taper, detoxification or transfer" phase (weeks 9-12).

      During the first week of induction onto methadone, participants will be administered fixed
      increasing doses of methadone starting at 30 mg daily and increased 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. 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 receive levetiracetam 500mg/day 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 8.

      At the end of week 8, participants will undergo detoxification from methadone over a 4-week
      period (weeks 8-12) 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 reported medication side
      effects (medication tolerability), and 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.
      This study will occur at the Outpatient Treatment Research Program in Building 36 at the VA
      CT Healthcare System.
    

Intervention name(s): levetiracetam
Intervention type(s): 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 not be blind to the subject's medication administration. The medication will be discontinued over a two-week period
Other intervention name(s): Keppra
Intervention MeSH terms: Levetiracetam
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: cocaine; opioids; heroin; levetiracetam