Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Annie Umbricht, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01137890
First received: June 3, 2010
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Cocaine Dependence
Drug: Zonisamide
Drug: Placebo
Drug: Cocaine Hydrochloride
Behavioral: Neurocognitive and Performance Battery
Behavioral: Smoking Assessments
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • subjective and objective measures of drug effect [ Time Frame: repeated interval during self-administration sessions ] [ Designated as safety issue: Yes ]
  • Behavioral Choice measures [ Time Frame: self-administration sessions ] [ Designated as safety issue: No ]
  • Cocaine selective severity assessment (measure of cocaine craving) [ Time Frame: daily ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Medication side-effects [ Time Frame: daily ] [ Designated as safety issue: Yes ]
  • smoking behaviors [ Time Frame: week-end days ] [ Designated as safety issue: No ]
  • neurocognitive assessment [ Time Frame: every other week ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: June 2010
Study Completion Date: August 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zonisamide
Participants administered blind capsules containing either placebo or zonisamide.
Drug: Zonisamide
Eight capsules administered daily in split doses at 22:00 and 09:00.
Other Names:
  • Zonegran,
  • CAS 68291-97-4,
Drug: Cocaine Hydrochloride
Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring.
Other Names:
  • CAS 50-36-2
  • methylbenzoylecgonine
  • benzoylmethylecgonine
  • C17H21NO4
Behavioral: Neurocognitive and Performance Battery
Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment.
Behavioral: Smoking Assessments
Participants answer questions about smoking and smoking behaviors are monitored.
Placebo Comparator: Placebo
Participants administered only placebo capsules containing lactose.
Drug: Placebo
capsules administered in split doses at 22:00 and 09:00.
Drug: Cocaine Hydrochloride
Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring.
Other Names:
  • CAS 50-36-2
  • methylbenzoylecgonine
  • benzoylmethylecgonine
  • C17H21NO4
Behavioral: Neurocognitive and Performance Battery
Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment.
Behavioral: Smoking Assessments
Participants answer questions about smoking and smoking behaviors are monitored.

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 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.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age at least 21 years old, not older than 45 years.
  • Evidence of cocaine dependence.
  • Not seeking treatment for cocaine abuse.
  • Able and willing to be restricted to our unit for 6-7 weeks.
  • Able to answer frequent questionnaires reliably and consistently.
  • Smoker.

Exclusion Criteria:

  • Allergy to Sulfonamide drugs (e.g. topiramate, zonisamide, sulfamethoxazole/trimethoprim).
  • Diabetes, respiratory insufficiency, renal tubular acidosis or renal insufficiency, heart failure, liver insufficiency, chronic diarrhea, other chronic diseases predisposing to acidosis.
  • Renal insufficiency defined as serum creatine > 1.30 mg/DL for males or > 1.03 mg/DL for females.
  • History of nephrolithiasis, unexplained hematuria on screening urinalysis.
  • History of head injury (with loss of consciousness longer than a few minutes).
  • History of seizure, or use of antiepileptic medications.
  • HIV positive individuals who meet AIDS by CDC criteria or are on antiretroviral medications.
  • BMI < 19 or BMI > 34.
  • Total cholesterol > 240mg%.
  • Serous psychiatric illness with psychosis, dementia.
  • Glaucoma, family history of glaucoma, one-sided blindness.
  • For female participants: being pregnant, lactating or not using an effective method of contraception.
  • Physical dependence on any drug other than cocaine, nicotine, or caffeine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01137890

Locations
United States, Maryland
Behavioral Pharmacology Research Unit
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Annie Umbricht, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: Annie Umbricht, Assistant Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01137890     History of Changes
Other Study ID Numbers: R01DA027065, R01DA027065
Study First Received: June 3, 2010
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
cocaine
addiction
drug dependence
anticonvulsant
zonisamide
drug self-administration
nicotine withdrawal
neurocognition

Additional relevant MeSH terms:
Cocaine
Zonisamide
Anesthetics
Anesthetics, Local
Anticonvulsants
Antioxidants
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sensory System Agents
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on October 23, 2014