Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)
Condition: Epilepsy, Partial; Epilepsy, Localization Related
MeSH terms: Epilepsy; Epilepsies, Partial
Intervention: Oxcarbazepine; Levetiracetam; Lamotrigine
Intervention description: Titration to target dose starting at week 3. Dose increments above target may be made to a maximum of 3 increments with a minimum interval between dose escalations of 2 weeks.; Titration to target dose starting at week 3. Dose increments above target may be made to a maximum of 3 increments with a minimum interval between dose escalations of 2 weeks.; Titration to target dose starting at week 11. Dose increments above target may be made to a maximum of 3 increments with a minimum interval between dose escalations of 2 weeks.
Intervention MeSH terms: Lamotrigine; Oxcarbazepine; Levetiracetam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 72.0
Sex: All
Minimum age: 5 Years
Maximum age: 16 Years
Healthy volunteers: No
Keywords: Pediatrics

Summary:

      Seizures that arise in specific areas in the brain are called Localization Related Epilepsy
      (LRE) and are the most common seizure disorder in children. Children that receive drug
      treatment for this disorder may suffer from treatment related side effects which impact their
      ability to think or concentrate and their ability to interact socially. These negative
      treatment effects can impact the child's performance in school and long term may impact
      employment and job options.

      This study will determine whether changes in attention and social interactions are seen in
      children treated for LRE using three of the most common medications used to treat pediatric
      LRE. Children who are newly diagnosed with LRE by their doctors and are between the ages of 5
      years 6 months and 16 years 0 months will be randomized to receive levetiracetam,
      lamotrigine, or oxcarbazepine.

      There will be 14 study sites throughout the US. Children will undergo evaluation of their
      thinking and ability to pay attention before and after starting drug treatment for LRE.
      Regardless of the specific findings, results of this study will provide the information
      needed to help parents and their clinicians choose treatment options that maximize cognitive
      abilities in children with LRE, and provide the data needed for practice guidelines to be
      established on the basis of cognitive side effect risks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age of participant between 5 years, 6 months and 16 years, 0 months at the time of
             enrollment

          -  Weight is between ≥ 15 kg the lower limit BMI 99th percentile at study entry at study
             entry

          -  Child has diagnosed epilepsy as defined by one of the following definitions :

               -  At least two unprovoked seizures occurring more than 24-hours apart, or

               -  One unprovoked seizure and a probability of further seizures similar to the
                  general recurrence risk after two unprovoked seizures (approximately 75% or
                  more), or

               -  At least two seizures in a setting of reflex epilepsy

          -  Child has a diagnosis of Localization Related Epilepsy (LRE) with or without secondary
             generalization according to International League Against Epilepsy (ILAE) criteria and
             which may include Benign Rolandic Epilepsy and Benign Occipital Epilepsy or other
             LREs.

          -  Localization related seizures will be based upon at least one of the following: 1)
             focal EEG abnormalities (sharp waves, spikes, or slowing) and the absence of
             generalized spike waves discharges, 2) focal MRI abnormalities other than active
             cysticercosis, which may include temporal lobe sclerosis, dysembryoplastic
             neuroepithelial tumor , ganglioglioma, or focal malformations of cortical development,
             3) focal neurologic abnormalities, or 4) clinical semiology, which may include Todd's
             phenomenon, unilateral dystonia, or fencing posture, or distinct aura consistent with
             localization related seizure onset (e.g., classic déjà vu or bad smell).

          -  Participants must either be antiepileptic drug (AED) therapy naïve or on an AED
             (excluding benzodiazepines) for 1-week or less. Children may be on a stable dose of
             psychostimulants at the time of enrollment, but no change in medication, dose, or
             schedule in 3 months prior to study enrollment, with no anticipated dosing changes
             during the 6 months of the study. If participants are taking psychostimulants at the
             time of study entry, they should plan on continuing them for the 6 month duration of
             the study protocol including the 3-month and 6-month cognitive and behavioral testing
             time points.

          -  Females of child bearing potential must agree to acceptable forms of birth control,
             which may include abstinence.

          -  The child's parent/guardian must be able to keep an accurate seizure diary and be able
             and willing to comply with instructions and study procedures.

          -  Informed consent from the child's legal guardian or legal representative.

          -  Assent will be obtained from children according to each site's institutional
             guidelines.

        Exclusion Criteria:

          -  Children with history of primary generalized seizures (absence, myoclonic, drop)

          -  Children with mixed seizure disorder (e.g., Lennox-Gastaut Syndrome)

          -  Children with sensory seizures only (i.e., auras)

          -  Children with 6+ seizures in the previous week

          -  Children with a history of status epilepticus

          -  Children with a history of neonatal seizures

          -  Children with diagnoses of pervasive developmental disorders (e.g., autism/autism
             spectrum disorders)

          -  Children with progressive neurological disease (e.g., degenerative, progressive
             neoplasm)

          -  Children with major medical disease (e.g., Insulin-Dependent Diabetes Mellitus (IDDM),
             cancer, renal failure)

          -  Children with diseases with cognitive impact (e.g., inborn errors of metabolism,
             sickle cell disease with history of stroke)

          -  Children with active cysticercosis documented on MRI

          -  Children with cognitive impairment of sufficient severity that, in the opinion of the
             investigator, would diminish the likelihood of valid test performance (roughly
             corresponding to Full Scale Intelligence Quotient (FSIQ) less than 70)

          -  Children with suicide attempt(s) at any point during their lifetime

          -  Children with active suicide ideation

          -  Children with chronic use of first generation antihistamines

          -  Children using recreational drugs (including alcohol)

          -  Children not fluent in either English or Spanish

          -  Female children who are pregnant

          -  Female children who are using oral contraceptives for birth control or for any other
             indication (e.g. acne treatment)