This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This research study is a randomized, double blind, comparative trial of ethosuximide (ETX), lamotrigine (LTG) and valproic acid (VPA) as initial monotherapy for children with Childhood Absence Epilepsy (CAE). Treatment success will be defined as a composite of seizure control and short and long-term tolerability. Freedom from failure rate will be the primary endpoint. Each anticonvulsant's impact on cognition (especially attention), behavior, and quality of life will be assessed through formal neuropsychological testing and validated questionnaires. Each patient's epilepsy syndrome will be extensively phenotyped with video EEGs. Individual systemic drug exposures, determined using a population pharmacokinetic (PK) approach, will define the impact of interpatient variability in drug disposition on antiepileptic drug (AED) efficacy and toxicity, and will be utilized in pharmacogenetic (PG) correlative studies of select drug metabolizing enzymes. The relationship between the response to AED therapy and polymorphic variation in the T type calcium channel AED binding site genes ( 1H, 1I subunits) or the AED-efflux transporter gene (ABCB1) will be investigated. Factors potentially predictive for the most common treatment limitations of each AED will be studied, including the PG, PK and clinical profiles of patients developing LTG associated rash, VPA induced weight gain or ETX associated gastrointestinal side effects.This trial represents the first and only large scale purely pediatric, randomized, double blind, comparative clinical trial for CAE (specifically) and pediatric epilepsy (in general) in the US. The results will answer an important, highly relevant, clinical question and directly impact upon clinical care nationwide for children with CAE.
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