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

• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Focal Epilepsy	Drug: Levetiracetam; Drug: Carabamazepine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: September 2011
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: February 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Levetiracetam	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.
Active Comparator: Carabamazepine	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.

Outcome Measures

Primary Outcome Measures :

1. 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))

Secondary Outcome Measures :

1. 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)

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Korea, Republic of

Severance hospital

Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

Yonsei University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT02208492 History of Changes
• Other Study ID Numbers: 4-2011-0365
• First Posted: August 5, 2014
• Last Update Posted: December 9, 2014
• Last Verified: December 2014

Keywords provided by Yonsei University:

Levetiracetam, Carabamazepine

Additional relevant MeSH terms:

Epilepsies, Partial; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carbamazepine; Levetiracetam; Anticonvulsants; Nootropic Agents; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers