Brief Summary
The purpose of this study is to determine the best initial treatment for childhood absence epilepsy.
Brief Title
Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Childhood Absence Epilepsy
Petit Mal Epilepsy
Epilepsy
Seizures
Eligibility 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.
* 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.
Inclusion 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).
* 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).
Gender
All
Gender Based
false
Keywords
childhood absence epilepsy
CAE
petit mal epilepsy
epilepsy
seizures
ethosuximide
lamotrigine
valproic acid
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
13 Years
Minimum Age
30 Months
NCT Id
NCT00088452
Org Class
Other
Org Full Name
Children's Hospital Medical Center, Cincinnati
Org Study Id
U01NS045911
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Participants With Freedom From Treatment Failure at 16-20 Weeks of Double Blind Therapy
Outcome Time Frame
First 16-20 weeks of double blind therapy
Secondary Ids
Secondary Id
U01NS045803
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
First 16-20 weeks of double blind therapy
Outcome Measure
Number of Participants With Attention Deficit as Measured by the Confidence Index of the CPT-II and the K-CPT
Outcome Description
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.
Outcome Time Frame
First 12 months of double blind therapy
Outcome Measure
Number of Participants With Freedom From Treatment Failure at 12 Months of Double Blind Therapy
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
13
Minimum Age Number (converted to Years and rounded down)
2
Investigators
Investigator Type
Principal Investigator
Investigator Name
Shlomo Shinnar
Investigator Email
sshinnar@montefiore.org
Investigator Phone