Clinical Trial of Topiramate for Cocaine Addiction
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders; Behavior, Addictive
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an outpatient clinical trial of topiramate for addressing cocaine dependence and
      reduction of cocaine associated behaviors in opiate dependent drug users maintained on
      methadone treatment.

      The study aims to answer whether topiramate

        1. is safe and acceptable to methadone patients

        2. reduces cocaine use

        3. helps with collateral problems such as alcohol abuse, tobacco dependence, anxiety, PTSD
           and/or pain symptoms. The study will also evaluate topiramate effect on neuro-cognitive
           performance.
    

Detailed description: 
      This is an outpatient clinical trial of topiramate treatment for cocaine dependence and
      reduction of cocaine-associated HIV risk behavior. Topiramate is of high current interest in
      this regard, having been identified my National Institute on Drud Abuse (NIDA) leadership as
      among only a small number of tested candidates providing a "positive signal" and warranting
      further clinical investigation (Vocci, 2005). Topiramate is a marketed antiepileptic that
      enhances the GABAergic system and antagonizes the glutamatergic system, both new targets in
      the search for anti-cocaine treatments. A published pilot trial has supported topiramate's
      efficacy, and it is especially intriguing as potentially beneficial against other disorders
      prevalent among drug users, such as mood, anxiety, panic disorders, PTSD, pain and cognitive
      dysfunction, that may contribute to drug use. Design/Methods: This is phase II, double-blind
      randomized (stratified) 4 group, 2x2 design, evaluating topiramate versus placebo under each
      of two levels of cocaine-abstinence motivation -- cocaine-abstinence-contingent versus
      non-contingent voucher incentives. Conduct will be in a methadone maintenance context to
      ensure adequate retention and adherence, with participants dually dependent on opioids and
      cocaine. The target topiramate stabilization dose is 300 mg/day (150 mg b.i.d.), with one
      dose per day being observed at the clinic. The voucher-incentive manipulation provides
      valuable information about the role of motivation in modulating medication effects; it also
      provides a positive control condition to document the sensitivity of the study methods for
      detecting therapeutic benefit. Enrollment will be 300 patients ( 240 completers, 60/group).
      Participation will be up to 33 weeks - Baseline/Placebo-Run-in (5 weeks), Randomized
      Medication Treatment (20 weeks, induction, stable dosing, taper), Randomized Voucher
      Treatment (12 weeks, embedded in Medication period), and Therapeutic Disposition (up to 8
      weeks). Data analysis focuses on the 8-week period of stable dosing and concurrent vouchers.
      The primary outcome variable is days abstinent from cocaine, as determined by a combination
      of self-report and objective confirmation by quantitative urinalysis toxicology of cocaine
      metabolite levels and application of the "Preston" rule for determining abstinence. Secondary
      outcome variables are measures of adverse behaviors and symptoms commonly co-occurring in
      cocaine abusers (alcohol abuse, tobacco use, depression, anxiety, PTSD, pain, neuro-cognitive
      and psychomotor performance dysfunction) that may contribute to drug use and/or detrimental
      effects. Significance: This randomized controlled clinical trial will provide valuable
      information about the actions and therapeutic effectiveness of the promising candidate
      anti-cocaine pharmacotherapy topiramate, and about the conditions, correlates, and modulators
      of any observed effectiveness. It will also provide valuable methodological information
      contributing to the continuing evolution of clinical trial methods for evaluating potential
      drug abuse treatment medications.
    

Intervention name(s): topiramate; Contingency Reinforcement; placebo + NonCR
Intervention type(s): Drug; Behavioral; Drug
Intervention description(s): topiramate powder 0mg - 150 mg with lactate in blind capsules. Two capsules dispensed daily. One capsule ingested under supervision at the methadone window. One capsule to be ingested at home at bedtime. Participant is expected to return the empty blister pack on the following day.
capsules are administered from week 4 through 25 of the trial; monetary reward for self-reported cocaine abstinence confirmed by urine toxicology results; participant receives placebo capsules and monetary reinforcers by chance, irrespective of cocaine use or abstinence
Other intervention name(s): topamax®; CAS 97240-79-4; contingency management
Intervention MeSH terms: Topiramate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: addiction; drug dependence; stimulant