Clinical trial NCT01891890: Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)
Official title: Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepsy, Partial
Epilepsy, Localization Related
Keywords: Pediatrics
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2013-07-03
Enrollment: 72
Sex: ALL
Minimum age (years): 5
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a prospective multicenter, randomized, open-label, central assessor, parallel-group study of children ages 5 years, 6 months to 16 years, 0 months with newly diagnosed Localization Related Epilepsy (LRE) to establish whether three common antiepileptic drugs (AEDs) used as first line LRE treatment (lamotrigine (LTG), levetiracetam (LEV), or oxcarbazepine (OXC)) are associated with differential cognitive side effects on attention. It is predicted that one AED will be identified with greater negative cognitive effects on attention. The study will also examine whether there are differential risks for drug-related behavior change. The study will address whether 6 month attentional outcomes can be reliably predicted based upon shorter term cognitive change assessed soon after beginning AED therapy, and establish practice effects associated with repeated test exposure when on constant doses of AED.

Children will undergo cognitive testing after study enrollment and no more than a week after AED initiation. Selected measures will be repeated at the first follow up clinic visit after beginning AED treatment, and the primary endpoint will be the attention performance obtained at the subjects' 6 month follow-up clinic visit.

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)

Primary outcomes:
measure: Conners' Continuous Performance Test II (CPT-II) Confidence Index
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Child Behavior Checklist
timeFrame: Baseline, Month 6
Other outcomes:
measure: Wechsler Intelligence Scale for Children-IV Processing Speed
timeFrame: Baseline, Month 3, Month 6
measure: Story Memory
timeFrame: Baseline, Month 6
measure: Symbol Digit Modalities Test
timeFrame: Month 3, Month 6
measure: Grooved Pegboard
timeFrame: Baseline, Month 6
measure: The Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Month 3, Month 6
measure: Youth Self Report
timeFrame: 6 months
measure: Affective Reactivity Scale
timeFrame: Baseline, Month 3, Month 6
measure: Pediatric Neuro-QOL Score
timeFrame: Baseline, Month 6
measure: Parenting Stress Inventory Short Form (PSI-4-SF)
timeFrame: Baseline, Month 6
measure: Pediatric Inventory for Parents
timeFrame: Baseline, Month 6
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Children's Healtcare of Atlanta
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Monroe
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Emory University
name: David W. Loring, PhD
role: PRINCIPAL_INVESTIGATOR
References: