Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)

NCT ID: NCT01891890

Last Updated: 2017-09-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2015-10-23

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.

Conditions

Epilepsy, Partial; Epilepsy, Localization Related

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Lamotrigine

Lamotrigine 7.0 mg/kg tablets or chewable tablets administered daily in 2 equally divided doses

Group Type: ACTIVE_COMPARATOR

Lamotrigine

Intervention Type: DRUG

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.

Oxcarbazepine

Oxcarbazepine 25 mg/kg tablets or liquid administered daily in 2 equally divided doses

Group Type: ACTIVE_COMPARATOR

Oxcarbazepine

Intervention Type: DRUG

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.

Levetiracetam

Levetiracetam 30 mg/kg tablet or liquid administered daily in 2 equally divided doses

Group Type: ACTIVE_COMPARATOR

Levetiracetam

Intervention Type: DRUG

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.

Interventions

Oxcarbazepine

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.

Intervention Type: DRUG

Levetiracetam

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.

Intervention Type: DRUG

Lamotrigine

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 Type: DRUG

Other Intervention Names

Trileptal; Keppra; Lamictal

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)

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

David Loring, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David W. Loring, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

University of California at San Diego

San Diego, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Healtcare of Atlanta

Atlanta, Georgia, United States

Johns Hopkins University

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

University of Rochester

Monroe, New York, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Le Bonheur Children's Hospital

Memphis, Tennessee, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Other Identifiers

PCORI 527

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB00066541

Identifier Type: -

Identifier Source: org_study_id