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Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

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ClinicalTrials.gov Identifier: NCT00088452
Recruitment Status : Completed
First Posted : July 27, 2004
Last Update Posted : February 6, 2017
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Study Description
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Brief Summary:
The purpose of this study is to determine the best initial treatment for childhood absence epilepsy.

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

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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 453 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
Actual Study Start Date : July 2004
Actual Primary Completion Date : January 2013
Actual Study Completion Date : August 31, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. treatment failure [ Time Frame: evaluated during study period 2 weeks to 5 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. CBCL--for behavior. [ Time Frame: evaluated during study period, 2 weeks to 5 years ]
  3. QOLCE--for quality of life. [ Time Frame: evaluated during study period, 2 weeks to 5 years ]
  4. Freedom from seizures. [ Time Frame: evaluated during study period, 2 weeks to 5 years ]
  5. Having a treatment-limiting adverse event. [ Time Frame: evaluated during study period, 2 weeks to 5 years ]
  6. Drug exposure levels and metabolite levels. [ Time Frame: evaluated during study period, 2 weeks to 5 years ]

Eligibility Criteria
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Ages Eligible for Study:   30 Months to 13 Years   (Child)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00088452     History of Changes
Other Study ID Numbers: U01NS45911; U01NS045803
First Posted: July 27, 2004    Key Record Dates
Last Update Posted: February 6, 2017
Last Verified: February 2017

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