Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
2 other identifiers
interventional
453
1 country
31
Brief Summary
The purpose of this study is to determine the best initial treatment for childhood absence epilepsy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2004
Longer than P75 for phase_3
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2004
CompletedFirst Submitted
Initial submission to the registry
July 26, 2004
CompletedFirst Posted
Study publicly available on registry
July 27, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2016
CompletedResults Posted
Study results publicly available
October 14, 2020
CompletedOctober 14, 2020
February 1, 2017
8.5 years
July 26, 2004
August 21, 2020
September 18, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With Freedom From Treatment Failure at 16-20 Weeks of Double Blind Therapy
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.
First 16-20 weeks of double blind therapy
Secondary Outcomes (2)
Number of Participants With Attention Deficit as Measured by the Confidence Index of the CPT-II and the K-CPT
First 16-20 weeks of double blind therapy
Number of Participants With Freedom From Treatment Failure at 12 Months of Double Blind Therapy
First 12 months of double blind therapy
Study Arms (3)
Ethosuximide
ACTIVE COMPARATOREthosuximide 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)
Lamotrigine
ACTIVE COMPARATORLamotrigine 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).
Valproic acid
ACTIVE COMPARATORValproic 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
Ethosuximide is a common treatment for childhood absence epilepsy.
Lamotrigine is a common treatment for childhood absence epilepsy.
Valproic acid is a common treatment for childhood absence epilepsy.
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
The Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
University of California at San Diego
La Jolla, California, 92093, United States
Mattel Children's Hospital at UCLA
Los Angeles, California, 90095, United States
Children's Hospital of Denver
Denver, Colorado, 80218, United States
Yale University School of Medicine
New Haven, Connecticut, 06520, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Nemours Children's Clinic
Jacksonville, Florida, 32207, United States
Miami Children's Hospital
Miami, Florida, 33155, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30342, United States
Children's Memorial Hospital
Chicago, Illinois, 60614, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Washington University in St. Louis
St Louis, Missouri, 63110, United States
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222, United States
NYU Comprehensive Epilepsy Center, Manhattan
New York, New York, 10016, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229, United States
Rainbow Babies & Children's Hospital
Cleveland, Ohio, 44106, United States
Children's Hospital, Inc., PCTI
Columbus, Ohio, 43205, United States
Doernbecher Children's Hospital
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
LeBonheur Children's Medical Center
Memphis, Tennessee, 38103, United States
Dallas Pediatric Neurology Associates
Dallas, Texas, 75230, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
University of Utah/Primary Children's Medical Center
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughter (Monarch Medical Research)
Norfolk, Virginia, 23510, United States
Children's Hospital & Regional Medical Center
Seattle, Washington, 98105-0371, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53201-1997, United States
Related Publications (5)
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.
PMID: 23167925BACKGROUNDCnaan 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.
PMID: 27986874BACKGROUNDShinnar 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.
PMID: 26311751BACKGROUNDGlauser 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.
PMID: 20200383RESULTShinnar 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.
PMID: 28916534DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This short-term study was not designed to detect long-term systemic or other cognitive effects of these three medications.
Results Point of Contact
- Title
- Tracy Glauser, MD
- Organization
- Cincinnati Children's Hospital Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Tracy A. Glauser, MD
Children's Hospital Medical Center, Cincinnati
- PRINCIPAL INVESTIGATOR
Peter Adamson, MD
Children's Hospital of Philadelphia
- PRINCIPAL INVESTIGATOR
Avital Cnaan, PhD
Children's National Research Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2004
First Posted
July 27, 2004
Study Start
July 1, 2004
Primary Completion
January 1, 2013
Study Completion
August 31, 2016
Last Updated
October 14, 2020
Results First Posted
October 14, 2020
Record last verified: 2017-02