Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
NCT ID: NCT00088452
Last Updated: 2020-10-14
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
453 participants
INTERVENTIONAL
2004-07-31
2016-08-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Ethosuximide
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
Ethosuximide is a common treatment for childhood absence epilepsy.
Lamotrigine
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
Lamotrigine is a common treatment for childhood absence epilepsy.
Valproic acid
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
Valproic acid is a common treatment for childhood absence epilepsy.
Interventions
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Ethosuximide
Ethosuximide is a common treatment for childhood absence epilepsy.
Lamotrigine
Lamotrigine is a common treatment for childhood absence epilepsy.
Valproic acid
Valproic acid is a common treatment for childhood absence epilepsy.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
30 Months
13 Years
ALL
Yes
Sponsors
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National Institute of Neurological Disorders and Stroke (NINDS)
NIH
Children's Hospital Medical Center, Cincinnati
OTHER
Responsible Party
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Principal Investigators
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Tracy A. Glauser, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital Medical Center, Cincinnati
Peter Adamson, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital of Philadelphia
Avital Cnaan, PhD
Role: PRINCIPAL_INVESTIGATOR
Children's National Research Institute
Locations
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The Children's Hospital of Alabama
Birmingham, Alabama, United States
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
University of California at San Diego
La Jolla, California, United States
Mattel Children's Hospital at UCLA
Los Angeles, California, United States
Children's Hospital of Denver
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
Miami Children's Hospital
Miami, Florida, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Children's Memorial Hospital
Chicago, Illinois, United States
Children's Hospital of Michigan
Detroit, Michigan, United States
Washington University in St. Louis
St Louis, Missouri, United States
Women and Children's Hospital of Buffalo
Buffalo, New York, United States
NYU Comprehensive Epilepsy Center, Manhattan
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
Rainbow Babies & Children's Hospital
Cleveland, Ohio, United States
Children's Hospital, Inc., PCTI
Columbus, Ohio, United States
Doernbecher Children's Hospital
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
LeBonheur Children's Medical Center
Memphis, Tennessee, United States
Dallas Pediatric Neurology Associates
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
University of Utah/Primary Children's Medical Center
Salt Lake City, Utah, United States
Children's Hospital of The King's Daughter (Monarch Medical Research)
Norfolk, Virginia, United States
Children's Hospital & Regional Medical Center
Seattle, Washington, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Adamson PC; Childhood Absence Epilepsy Study Team. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia. 2013 Jan;54(1):141-55. doi: 10.1111/epi.12028. Epub 2012 Nov 21.
Cnaan A, Shinnar S, Arya R, Adamson PC, Clark PO, Dlugos D, Hirtz DG, Masur D, Glauser TA; Childhood Absence Epilepsy Study Group. Second monotherapy in childhood absence epilepsy. Neurology. 2017 Jan 10;88(2):182-190. doi: 10.1212/WNL.0000000000003480. Epub 2016 Dec 16.
Shinnar S, Cnaan A, Hu F, Clark P, Dlugos D, Hirtz DG, Masur D, Mizrahi EM, Moshe SL, Glauser TA; Childhood Absence Epilepsy Study Group. Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial. Neurology. 2015 Sep 29;85(13):1108-14. doi: 10.1212/WNL.0000000000001971. Epub 2015 Aug 26.
Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Capparelli EV, Adamson PC; Childhood Absence Epilepsy Study Group. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010 Mar 4;362(9):790-9. doi: 10.1056/NEJMoa0902014.
Shinnar RC, Shinnar S, Cnaan A, Clark P, Dlugos D, Hirtz DG, Hu F, Liu C, Masur D, Weiss EF, Glauser TA; Childhood Absence Epilepsy Study Group. Pretreatment behavior and subsequent medication effects in childhood absence epilepsy. Neurology. 2017 Oct 17;89(16):1698-1706. doi: 10.1212/WNL.0000000000004514. Epub 2017 Sep 15.
Provided Documents
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Document Type: Informed Consent Form
Other Identifiers
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