Clinical trial NCT00088452
Conditions: Childhood Absence Epilepsy Petit Mal Epilepsy Epilepsy Seizures
Keywords: childhood absence epilepsy CAE petit mal epilepsy epilepsy seizures ethosuximide lamotrigine valproic acid
Sponsor: Children's Hospital Medical Center, Cincinnati
Start date: 2004-07-01; Completion date: 2016-08-31
Enrollment: 453 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the best initial treatment for childhood absence epilepsy.

Detailed description:
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.

Arms: arm 1: 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) arm 2: 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). arm 3: 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)
Interventions: intervention 1: Ethosuximide intervention 2: Lamotrigine intervention 3: Valproic acid
Intervention descriptions: intervention 1: Ethosuximide is a common treatment for childhood absence epilepsy. intervention 2: Lamotrigine is a common treatment for childhood absence epilepsy. intervention 3: Valproic acid is a common treatment for childhood absence epilepsy.

Protocol documents: