Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse
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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 |
- 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 ]
- 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 ]
| Estimated Enrollment: | 50 |
| Study Start Date: | June 2010 |
| Estimated Study Completion Date: | August 2012 |
| Estimated Primary Completion Date: | August 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:
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:
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:
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 |
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| Contact: Sarah Ilk | 410-550-0159 | silk1@jhmi.edu |
| Contact: Julia Kane | 410-550-2799 | jkane23@jhmi.edu |
| United States, Maryland | |
| Behavioral Pharmacology Research Unit | Recruiting |
| Baltimore, Maryland, United States, 21224 | |
| Contact: Jessica Vanderhoff 410-550-2799 jvande20@jhmi.edu | |
| Contact: Sarah Ilk 410-550-0159 silk1@jhmi.edu | |
| Principal Investigator: Annie Umbricht, MD | |
| Sub-Investigator: Porche K Henry, PhD | |
| Sub-Investigator: George E Bigelow, PhD | |
| Sub-Investigator: Miriam Mintzer, PhD | |
| Principal Investigator: | Annie Umbricht, M.D. | Johns Hopkins University |
More Information
No publications provided
| Responsible Party: | Annie Umbricht, M.D., Johns Hopkins University School of Medicine |
| ClinicalTrials.gov Identifier: | NCT01137890 History of Changes |
| Other Study ID Numbers: | R01DA027065, R01DA027065 |
| Study First Received: | June 3, 2010 |
| Last Updated: | June 21, 2011 |
| 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-Related Disorders Substance-Related Disorders Mental Disorders Cocaine Zonisamide Vasoconstrictor Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Dopamine Uptake Inhibitors Dopamine Agents Neurotransmitter Agents |
Molecular Mechanisms of Pharmacological Action Neurotransmitter Uptake Inhibitors Physiological Effects of Drugs Anesthetics, Local Anesthetics Central Nervous System Depressants Sensory System Agents Peripheral Nervous System Agents Central Nervous System Agents Antioxidants Protective Agents Anticonvulsants |
ClinicalTrials.gov processed this record on May 19, 2013