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

Condition	Treatment or Intervention	Phase
Childhood Absence Epilepsy Petit Mal Epilepsy Epilepsy Seizures	Drug: ethosuximide  Drug: lamotrigine  Drug: valproic acid	Phase III

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 20 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.

Ages Eligible for Study:  2 Years   -   13 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

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 < 90th 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 agree to a medically acceptable form of contraception (abstinence is a medically acceptable form) 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.
• Subject weighs > 31 kg and cannot swallow capsules.

Eileen Dorsey      215-590-1295    dorseye@email.chop.edu

Arkansas
      Arkansas Children’s Hospital, Little Rock,  Arkansas,  72202,  United States; Not yet recruiting
California
      Mattel Children’s Hospital at UCLA, Los Angeles,  California,  90095,  United States; Not yet recruiting
      University of California at San Diego, LaJolla,  California,  92093,  United States; Recruiting
Colorado
      Children’s Hospital of Denver, Denver,  Colorado,  80218,  United States; Recruiting
Connecticut
      Yale University School of Medicine, New Haven,  Connecticut,  06520,  United States; Not yet recruiting
District of Columbia
      Children’s National Medical Center, Washington,  District of Columbia,  20010,  United States; Not yet recruiting
Florida
      Miami Children’s Hospital, Miami,  Florida,  33155,  United States; Not yet recruiting
      Nemours Children’s Clinic, Jacksonville,  Florida,  32207,  United States; Recruiting
Illinois
      Children’s Memorial Hospital, Chicago,  Illinois,  60614,  United States; Recruiting
Michigan
      Children’s Hospital of Michigan, Detroit,  Michigan,  48201,  United States; Not yet recruiting
Missouri
      Washington University in St. Louis, St. Louis,  Missouri,  63110,  United States; Recruiting
New York
      Montefiore Medical Center, Bronx,  New York,  10467,  United States; Recruiting
Ohio
      Cincinnati Children’s Hospital, Cincinnati,  Ohio,  45229,  United States; Recruiting
      Children’s Hospital, Inc., PCTI, Columbus,  Ohio,  43205,  United States; Not yet recruiting
      Rainbow Babies & Children’s Hospital, ,, Cleveland,  Ohio,  44106,  United States; Not yet recruiting
Pennsylvania
      Children’s Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Not yet recruiting
      Children’s Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Texas
      University of Texas at Houston, Houston,  Texas,  77030,  United States; Not yet recruiting
      Texas Children’s Hospital, Houston,  Texas,  77030,  United States; Not yet recruiting
Virginia
      King’s Daughter (Monarch Research), Norfolk,  Virginia,  23510,  United States; Not yet recruiting

Study chairs or principal investigators

Tracy A. Glauser, MD,  Principal Investigator,  Associate Professor of Pediatrics and Neurology, Children’s Hospital Medical Center   
Peter Adamson, MD,  Principal Investigator,  Associate Professor of Pediatrics and Pharmacology, The Children’s Hospital of Philadelphia   
Avital Cnaan, PhD,  Principal Investigator,  Division Chief, Associate Professor of Pediatrics, Biostatistics, and Epidemiology, The Children’s Hospital of Philadelphia   

Study ID Numbers:  U01NS45911; U01NS045803
Record last reviewed:  July 2004
Record first received:  July 26, 2004
ClinicalTrials.gov Identifier:  NCT00088452
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08