Completed

Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

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What is being tested

Ethosuximide

+ Lamotrigine
+ Valproic acid
Drug
Who is being recruted

Epileptic Syndromes
+6

+ Brain Diseases
+ Central Nervous System Diseases
From 30 Months to 13 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: July 2004
See protocol details

Summary

Principal SponsorChildren's Hospital Medical Center, Cincinnati
Last updated: January 13, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: July 1, 2004Actual date on which the first participant was enrolled.

Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome that affects 10 to 15 percent of all children with epilepsy. Individuals with CAE have brief staring spell seizures that occur suddenly, unpredictably, and frequently throughout the day. These seizures impair the children's ability to learn and play, and lead to higher injury rates. There are many medications used to treat seizures, but only 3 generally are used as the first treatment for children with CAE: ethosuximide, lamotrigine, and valproic acid. The goal of this study is to determine which of these 3 medicines is the best first choice as treatment for children with CAE. Approximately 439 children, recruited over a 3-year period at 32 medical centers in the US, will take part in this 5-year study. Participants will be randomly given one of the 3 common CAE treatments-ethosuximide, lamotrigine, or valproic acid-and will make regular visits to a clinic every 1 to 3 months for approximately 2 years. During the visits, participants will undergo regular testing to determine if the medicine is working, to watch for side effects, and to help researchers learn more about the responses to these medicines. In addition, researchers hope to develop methods that may be used in the future to help choose the best medicine for each individual diagnosed with CAE. Also included in the study will be pharmacokinetics and pharmacogenetics research. Pharmacokinetics is the study of how the body absorbs, distributes, metabolizes, and excretes drugs. Pharmacogenetics is the study of genetic determinants of the response to drugs. Knowledge gained from this study may lead to individualized treatment for children with CAE, and may also be beneficial for other pediatric and adult seizure disorders.

Official TitleChildhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study 
NCT00088452U01NS045911
Principal SponsorChildren's Hospital Medical Center, Cincinnati
Last updated: January 13, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
453 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the interventions assigned to participants is kept confidential
Participants, researchers, and outcome assessors do not know which treatment is being given. This helps reduce bias not just during the study, but also when the results are being evaluated.

Other Ways to Mask Information
Open-label: Everyone knows which treatment is being given.
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 30 Months to 13 YearsRange of ages for which participants are eligible to join.
Healthy volunteers allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Epileptic Syndromes
Brain Diseases
Central Nervous System Diseases
Epilepsy
Epilepsy, Generalized
Epilepsy, Absence
Nervous System Diseases
Neurologic Manifestations
Seizures
Criteria

Inclusion Criteria: * Diagnosis: Clinical diagnosis of Childhood Absence Epilepsy consistent with the International League against Epilepsy Proposal for Revised Classification of Epilepsies and Epileptic Syndromes (3). * EEG: Interictal EEG demonstrating bilateral synchronous symmetrical approximate 3 Hz spike waves on a normal background with at least one burst lasting \>/= (greater than or equal to) 3 seconds. * Age \> 2.5 years and \< 13 years of age at study entry. * Body weight \>/= (greater than or equal to) 10 kilograms. * Body Mass Index: BMI for age =/\< 99th percentile (based on the CDC BMI for age growth curves for boys/girls \[http://www.cdc.gov/growthcharts\], Appendix 1). * Hepatic: * AST/ALT \< 2.5 times the upper limit of normal * Total bilirubin \< 1.5 times the upper limit of normal. * Hematologic: * Absolute neutrophil count \>/= (greater than or equal to) 1500/mm3. * Platelets \>/= (greater than or equal to) 120, 000 /mm3. * Female subjects must be premenarchal at the time of enrollment and must be willing to practice abstinence for the duration of the study. * Parent/legal guardian(s) willing to sign an IRB approved informed consent. * Subject assent (when appropriate and as dictated by local IRB). Exclusion Criteria: * Treatment for CAE with anti-seizure medications (AED) for a period of greater than 7 days prior to randomization. * History of a major psychiatric disease (e.g., psychosis, major depression). * History of autism or pervasive development disorder. * History of non-febrile seizures other than typical absence seizures. This includes a history of an afebrile generalized tonic clonic seizure. * Clinical signs and symptoms consistent with a diagnosis of juvenile absence epilepsy or juvenile myoclonic epilepsy as delineated by the International League against Epilepsy Proposal for Revised Classification of Epilepsies and Epileptic Syndromes (3). * History of recent or present significant or medical disease, i.e., cardiovascular, hepatic, renal, gynecologic, musculoskeletal, metabolic, or endocrine. * History of a severe dermatologic reaction (e.g., Stevens Johnson, toxic epidermolysis necrosis) to medication. * Subject or parent/legal guardian might not be reasonably expected to be compliant with or to complete the study. * Participation in a trial of an investigational drug or device within 30 days prior to screening. * Use of systemic contraceptive for any indication, including acne.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
3 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Active Comparator
Ethosuximide Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight and ability to swallow): 250mg Zarontin capsules OR 250 mg/5 mL Zarontin syrup Dosing: Ethosuximide was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 2000 mg/day (whichever was lower)

Ethosuximide is a common treatment for childhood absence epilepsy.
Group II
Active Comparator
Lamotrigine Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Three formulations were used (actual formulation used was dependent on the patient's weight): 5mg Lamictal chewable tablets OR 25 mg Lamictal chewable tablets OR 25 mg (Lamictal tablets Dosing: Lamotrigine was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 12 mg/kg/day or 600 mg/day (whichever was lower).

Lamotrigine is a common treatment for childhood absence epilepsy.
Group III
Active Comparator
Valproic acid Frequency and Duration: twice a day, every day for the duration of the study treatment Formulation: Two formulations were used (actual formulation used was dependent on the patient's weight): 250mg Depakote capsules OR 125mg Depakote sprinkles. Dosing: Depakote was titrated in predetermined increments every 1-2 weeks during a 16-week titration period. The titration continued until the patient a) achieved seizure freedom by clinical and EEG criteria, b) reached the maximal allowed study drug dose, c) reached the maximal tolerated dose, or d) developed dose-exiting criteria (treatment failure), whichever came first. Maximum allowed dose: 60 mg/kg/day or 3000 mg/day (whichever was lower)

Valproic acid is a common treatment for childhood absence epilepsy.
Study Objectives
Primary Objectives

Treatment failure was defined as persistence of absence seizures at week 16 or week 20, a generalized tonic-clonic seizure at any time, excessive drug-related systemic toxicity, a moderately severe rash (possibly drug-related), pancreatitis, or increase in the body-mass index of at least 3.0 from baseline, dose-limiting toxicity after a single downward dose modification, or withdrawal initiated by the parent or physician.
Secondary Objectives

A Confidence Index of 0.60 or higher on the Conners' Continuous Performance Test at the visit at 16 or 20 weeks or at an earlier visit when treatment was discontinued (as long as the discontinuation occurred 1 month or more after the baseline visit and was not due to intolerable adverse events). A Confidence Index of 0.60 corresponds to a 60% probability that the child has clinical attention deficit disorder.

Treatment failure was defined as persistence of absence seizures at 12 months of double blind therapy, a generalized tonic-clonic seizure at any time, excessive drug-related systemic toxicity, a moderately severe rash (possibly drug-related), pancreatitis, or increase in the body-mass index of at least 3.0 from baseline, dose-limiting toxicity after a single downward dose modification, or withdrawal initiated by the parent or physician.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 31 locations
Suspended
The Children's Hospital of AlabamaBirmingham, United StatesSee the location
Suspended
St. Joseph's Hospital and Medical CenterPhoenix, United States
Suspended
Arkansas Children's HospitalLittle Rock, United States
Suspended
University of California at San DiegoLa Jolla, United States
Completed31 Study Centers
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