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

Sponsor:	Children's Hospital Medical Center, Cincinnati
Collaborator:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT00088452

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment
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 pyridoxine-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

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

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
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

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

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

Responsible Party:	Cincinnati Children's Hospital Medical Center ( Tracy A. Glauser, MD, Professor of Pediatrics and Neurology and Director of the Comprehensive Epilepsy Program )
Study ID Numbers:	U01NS45911; U01NS045803
Study First Received:	July 26, 2004
Last Updated:	September 10, 2009
ClinicalTrials.gov Identifier:	NCT00088452 History of Changes
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:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Calcium Channel Blockers
Brain Diseases
Valproic Acid
Membrane Transport Modulators
Signs and Symptoms
Therapeutic Uses
Ethosuximide
Tranquilizing Agents
Nervous System Diseases
Seizures

Epilepsy, Absence
Central Nervous System Diseases
Central Nervous System Depressants
Enzyme Inhibitors
Cardiovascular Agents
Antimanic Agents
Pharmacologic Actions
Epilepsy
Lamotrigine
Neurologic Manifestations
GABA Agents
Epilepsy, Generalized
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on November 27, 2009