Clinical trial NCT01137890
Conditions: Cocaine Dependence
Keywords: cocaine addiction drug dependence anticonvulsant zonisamide drug self-administration nicotine withdrawal neurocognition
Sponsor: Johns Hopkins University
Start date: 2010-06-01; Completion date: 2013-08-01
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a residential pilot trial to evaluate the pharmacodynamic interaction between zonisamide and cocaine, with the goal of evaluating zonisamide's potential for the treatment of cocaine dependence.

Detailed description:
This is a residential pilot trial to evaluate the effect of zonisamide (ZNS) on cocaine reinforcement, craving and relapse. Cocaine addiction remains a major social and medical problem that imposes a significant burden on our society, as more than a half million cocaine dependent individuals are seeking treatment every year. Medications that act to antagonize the glutamate system and/or increase the GABA-system are new targets in the search towards effective cocaine treatment. ZNS is part of a new line of antiepileptic agents that act both as glutamate antagonists and to enhance the Gamma-AminoButyric acid (GABA) system. Topiramate, a similar agent, showed a positive signal in a pilot trial for cocaine dependence. ZNS has the advantages of a longer half-life requiring only once a day dosing and, being better tolerated, it requires a shorter induction phase and can be administered at higher doses. We hypothesize that ZNS in moderate to high doses will attenuate the central effect of cocaine and improve the neural perturbations resulting from cocaine use, thus decreasing cocaine craving. Healthy, adult cocaine dependent volunteers will be enrolled on our residential unit for 44 days for this double-blind within subject study. The pharmacodynamic interactions between ZNS and cocaine will be measured in cocaine self-administration procedure offering alternative reinforcers with monetary values. Cocaine reinforcing effect will be evaluated over a range of doses, and subjective and objective outcomes on mood and behavior will be collected. In addition, the effect of ZNS on ad-lib smoking will be studied on the days when no other procedure interferes with smoking behaviors. Neurocognitive and psychomotor effects of ZNS treatment will also be studied with an extensive test battery on the day of the week when no cocaine is administered. This study will explore the potential therapeutic effect of ZNS for the treatment of cocaine dependence while providing necessary safety assessments required for possible future outpatient clinical trials.

Arms: arm 1: Participants administered blind capsules containing either placebo or zonisamide. arm 2: Participants administered only placebo capsules containing lactose.
Interventions: intervention 1: Zonisamide intervention 2: Placebo intervention 3: Cocaine Hydrochloride intervention 4: Neurocognitive and Performance Battery intervention 5: Smoking Assessments
Intervention descriptions: intervention 1: Eight capsules administered daily in split doses at 22:00 and 09:00. intervention 2: capsules administered in split doses at 22:00 and 09:00. intervention 3: Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring. intervention 4: Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment. intervention 5: Participants answer questions about smoking and smoking behaviors are monitored.

Protocol documents: