Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE)

NCT01891890 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: IRB00066541PCORI 527
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 14

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.

Conditions

Epilepsy, Partial; Epilepsy, Localization Related

Keywords

Pediatrics

Outcome Measures

Primary Outcomes (1)

• Conners' Continuous Performance Test II (CPT-II) Confidence Index

  The Conners' Continuous Performance Test II (CPT-II) is a measure of sustained attention. Letters are individually presented on a computer screen, and participants are instructed to press the space bar when they are presented with any letter except the letter "X". For children younger than 6 years of age at enrollment, the Kiddie CPT will be used in which the child is instructed to press the space bar every time the ball appears on the screen. The outcome measure is a confidence index representing the probability that the respondent has a clinically relevant problem in sustained attention. Possible scores range from 0 to 100. Scores between 40 and 60 are considered inconclusive while scores above 60 indicate that the child exhibits inattentiveness.

  Baseline, Month 6

Secondary Outcomes (1)

• Child Behavior Checklist

  Baseline, Month 6

Other Outcomes (10)

• Wechsler Intelligence Scale for Children-IV Processing Speed

  Baseline, Month 3, Month 6

• Story Memory

  Baseline, Month 6

• Symbol Digit Modalities Test

  Month 3, Month 6

Study Arms (3)

Lamotrigine

ACTIVE COMPARATOR

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

Drug: Lamotrigine

Oxcarbazepine

ACTIVE COMPARATOR

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

Drug: Oxcarbazepine

Levetiracetam

ACTIVE COMPARATOR

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

Drug: Levetiracetam

Interventions

Oxcarbazepine 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.

Also known as: Trileptal

Oxcarbazepine

Levetiracetam 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.

Also known as: Keppra

Levetiracetam

Lamotrigine 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.

Also known as: Lamictal

Lamotrigine

Eligibility Criteria

• Age: 5 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (14)

Arkansas Children's Hospital

Little Rock, Arkansas, 72205, United States

Location

University of California at San Diego

San Diego, California, 92092, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healtcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Rochester

Monroe, New York, 14642, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38105, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

MeSH Terms

Conditions

Epilepsies, Partial

Interventions

Oxcarbazepine; Levetiracetam; Lamotrigine

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Carbamazepine; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Triazines

Limitations and Caveats

The study was terminated early due to inability to meet enrollment goals.

Results Point of Contact

• Title: David Loring, PhD
• Organization: Emory University

dloring@emory.edu

404-778-5943

Study Officials

• David W. Loring, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 28, 2013
• First Posted: July 3, 2013
• Study Start: August 1, 2013
• Primary Completion: October 23, 2015
• Study Completion: October 23, 2015
• Last Updated: September 19, 2017
• Results First Posted: September 19, 2017

Record last verified: 2017-07

Locations

US (14)