Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

Epilepsy Clinical Trial

Official title:

Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00088452
• Other study ID #: U01NS045911
• Secondary ID: U01NS045803
• Status: Completed
• Phase: Phase 3
• Start date: July 2004
• Est. completion date: August 31, 2016

Study information

• Verified date: February 2017
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 453
• Est. completion date: August 31, 2016
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Months to 13 Years

Eligibility

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.

Related Conditions & MeSH terms

• Childhood Absence Epilepsy
• Epilepsy
• Epilepsy, Absence
• Petit Mal Epilepsy
• Seizures

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	The Children's Hospital of Alabama	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	Children's Memorial Hospital	Chicago	Illinois
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	Dallas Pediatric Neurology Associates	Dallas	Texas
United States	Children's Hospital of Denver	Denver	Colorado
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	University of California at San Diego	La Jolla	California
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Mattel Children's Hospital at UCLA	Los Angeles	California
United States	LeBonheur Children's Medical Center	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Yale University School of Medicine	New Haven	Connecticut
United States	NYU Comprehensive Epilepsy Center, Manhattan	New York	New York
United States	Children's Hospital of The King's Daughter (Monarch Medical Research)	Norfolk	Virginia
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah/Primary Children's Medical Center	Salt Lake City	Utah
United States	Children's Hospital & Regional Medical Center	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. do — View Citation

Shinnar S, Cnaan A, Hu F, Clark P, Dlugos D, Hirtz DG, Masur D, Mizrahi EM, Moshé 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Attention Deficit as Measured by the Confidence Index of the CPT-II and the K-CPT	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.	First 16-20 weeks of double blind therapy
Secondary	Number of Participants With Freedom From Treatment Failure at 12 Months of Double Blind Therapy	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.	First 12 months of double blind therapy