The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study

• ClinicalTrials.gov Identifier: NCT02208492
• Recruitment Status: Completed
• First Posted: August 5, 2014
• Last Update Posted: December 9, 2014
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Tracking Information

• First Submitted Date: August 3, 2014
• First Posted Date: August 5, 2014
• Last Update Posted Date: December 9, 2014
• Study Start Date: September 2011
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2014)

Assessment and comparative analysis of initial and follow-up Neuropsychological evaluation in both treated groups. (Levetiracetam and Carbamazepine) [ Time Frame: 52 weeks ]

changes in a series of follow-up neurocognitive, behavioral, and emotional function tests (Korean Wechsler Intelligence Scale for Children-Third edition (K-WISC-III, for subjects 6-16 years old)19, 20 or the Korean Weschler Preschool and Primary Scale of Intelligence-Third edition (K-WIPSSI-III, for ages 4-6), Korean-Child Behavior Checklist (K-CBCL), Children's Depression Inventory (CDI) 24 and Revised Children's Manifest Anxiety Scale (RCMAS))

Original Primary Outcome Measures (submitted: August 3, 2014)

Seizure Outcome [ Time Frame: 6 months ]

The percentage of seizure free patients in the last six months period of the study

• Change History: Complete list of historical versions of study NCT02208492 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 8, 2014)

Seizure control efficacy [ Time Frame: 52 weeks ]

Comparison of baseline frequency to final follow-up frequency during the last 24 weeks of the maintenance period(at last visit at 52 week time point)

Original Secondary Outcome Measures (submitted: August 3, 2014)

Behavior assessment [ Time Frame: 1 year ]

Assessment of neuropsychological function of the patients on the study medication

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study
• Official Title: Not Provided

Brief Summary

Unlike the first generation antiepileptic medications, newer drugs for epilepsy such as levetiracetam are reported to have less adverse effect in children but not many studies have systematically reviewed the subject. This study aims to prospectively evaluate the effect of levetiracetam on neurocognition, behavioral issues and quality of life, as well as its seizure control efficacy and other adverse events in pediatric epilepsy patients, in comparison to carbamazepine, one of the classic antiepileptic medication, widely prescribed for both partial and generalized seizures, despite its well known side effects.

This multicenter, open-label, parallel-group trial is expected to enroll 130 patients from age 4 to 16 woh will be randomized into two groups, which will be prescribed with levetiracetam or carbamazepine. Series of neuropsychological assessment and behavioral and life evaluations of the patients will be performed at baseline period and after the 52 weeks of study period.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Focal Epilepsy

Intervention

• Drug: Levetiracetam
  Levetiracetam is a second-generation antiepileptic drug that has been approved for the treatment of epilepsy in both children and adults. This anticonvulsant works by binding to the synaptic vesicle protein 2A resulting in a possible effect on neurotransmitter release from presynaptic vesicles, while the exact mechanism of action is still unclear. In both adults and children, levetiracetam treatment in has a proven efficacy in both localization-related and generalized epilepsies. In contrast to first generation, levetiracetam reports less side effects of somnolence or lethargy, but behavioral adverse events, such as changed mood state, aggression, and irritability are noted, but only a few studies have reported such effects in a systemic fashion.
• Drug: Carabamazepine
  Carbamazepine, a first-generation antiepileptic medication, stabilizes the inactivated state of voltage-gated sodium channels, making fewer of these channels available to subsequently open, which leaves the affected cells less excitable and less seizure prone. It is approved for both focal seizures and generalized tonic-clonic or combined seizures for adults and children.

Study Arms

• Experimental: Levetiracetam
  Intervention: Drug: Levetiracetam
• Active Comparator: Carabamazepine
  Intervention: Drug: Carabamazepine

• Publications *: Jung DE, Yu R, Yoon JR, Eun BL, Kwon SH, Lee YJ, Eun SH, Lee JS, Kim HD, Nam SO, Kim GH, Hwang SK, Eom S, Kang DR, Kang HC. Neuropsychological effects of levetiracetam and carbamazepine in children with focal epilepsy. Neurology. 2015 Jun 9;84(23):2312-9. doi: 10.1212/WNL.0000000000001661. Epub 2015 May 6.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 3, 2014): 75
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: February 2014
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients from age 4 to 16, who have been diagnosed with focal epilepsy
2. Patients who have experienced minimal two unprovoked seizures, or patients who have had one unprovoked seizure and have shown focal abnormality in the EEG
3. Patients who have not received any antiepileptic medications prior to the study (Those who have been treated with rescue medication are eligible)
4. Patients with eligible consent or with legal guardians have given official consent

Exclusion Criteria:

1. Patients with progressive CNS disease, or systemic illness
2. Patients with level of SGOT/SPGT above the doubled normal level or BUN/Creatinine above the 3 times of the normal range
3. Patients who had used other anti-epileptic medication during any period of the trial, including baseline period. (Benzodiazepine used as rescue therapy is acceptable)
4. Patients who show hypersensitive reaction to the study medication.
5. Patients with any psychological problems.
6. Patients deemed inappropriate for the study by the investigators

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 16 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT02208492
• Other Study ID Numbers: 4-2011-0365
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Yonsei University
• Study Sponsor: Yonsei University
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Yonsei University
• Verification Date: December 2014