Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study - Full Text View

Purpose

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

Condition	Intervention	Phase
Childhood Absence Epilepsy Petit Mal Epilepsy Epilepsy Seizures	Drug: ethosuximide Drug: lamotrigine Drug: valproic acid	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

Drug Information available for: Ethosuximide Valproic acid Valproate sodium Divalproex sodium Lamotrigine

Genetic and Rare Diseases Information Center resources: Epilepsy Juvenile Absence

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:

treatment failure [ Time Frame: evaluated during study period 2 weeks to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Omission errors and the overall Confidence Index(CIOI)of the CPT-II and the K-CPT--for attention. [ Time Frame: evaluated during study period, 2 weeks to 5 years ] [ Designated as safety issue: Yes ]
CBCL--for behavior. [ Time Frame: evaluated during study period, 2 weeks to 5 years ] [ Designated as safety issue: Yes ]
QOLCE--for quality of life. [ Time Frame: evaluated during study period, 2 weeks to 5 years ] [ Designated as safety issue: Yes ]
Freedom from seizures. [ Time Frame: evaluated during study period, 2 weeks to 5 years ] [ Designated as safety issue: Yes ]
Having a treatment-limiting adverse event. [ Time Frame: evaluated during study period, 2 weeks to 5 years ] [ Designated as safety issue: Yes ]
Drug exposure levels and metabolite levels. [ Time Frame: evaluated during study period, 2 weeks to 5 years ] [ Designated as safety issue: Yes ]


Enrollment:	453
Study Start Date:	July 2004
Estimated Study Completion Date:	November 2014
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 ethosuximide	Drug: ethosuximide Ethosuximide is a common treatment for childhood absence epilepsy.
Active Comparator: 2 lamotrigine	Drug: lamotrigine Lamotrigine is a common treatment for childhood absence epilepsy.
Active Comparator: 3 valproic acid	Drug: valproic acid Valproic acid is a common treatment for childhood absence epilepsy.

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.

Eligibility


Ages Eligible for Study:	30 Months to 13 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088452

Show 31 Study Locations

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators


Principal Investigator:	Tracy A. Glauser, MD	Professor of Pediatrics and Neurology and Director of the Comprehensive Epilepsy Center, Cincinnati Children's Hospital Medical Center
Principal Investigator:	Peter Adamson, MD	Professor of Pediatrics and Pharmacology, Chief of Division of Clinical Pharmacology and Therapeutics, Director of Office of Clinical and Translational Research, Children's Hospital of Philadelphia
Principal Investigator:	Avital Cnaan, PhD	Director, Multi-Center Studies Section, Children's National Medical Center

More Information

No publications provided by Children's Hospital Medical Center, Cincinnati

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.


Responsible Party:	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT00088452 History of Changes
Other Study ID Numbers:	U01NS45911; U01NS045803
Study First Received:	July 26, 2004
Last Updated:	August 12, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Children's Hospital Medical Center, Cincinnati:


childhood absence epilepsy CAE petit mal epilepsy epilepsy	seizures ethosuximide lamotrigine valproic acid

Additional relevant MeSH terms:


Epilepsy Epilepsy, Absence Brain Diseases Central Nervous System Diseases Epilepsy, Generalized Nervous System Diseases Ethosuximide Lamotrigine Valproic Acid Anticonvulsants Antimanic Agents Calcium Channel Blockers Cardiovascular Agents Central Nervous System Agents Central Nervous System Depressants	Enzyme Inhibitors Excitatory Amino Acid Agents Excitatory Amino Acid Antagonists GABA Agents Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Pharmacologic Actions Physiological Effects of Drugs Psychotropic Drugs Sodium Channel Blockers Therapeutic Uses Tranquilizing Agents Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on February 27, 2015