Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00088452
First received: July 26, 2004
Last updated: August 12, 2014
Last verified: March 2013
  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:


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

  Hide Study Locations
Locations
United States, Alabama
The Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
University of California at San Diego
LaJolla, California, United States, 92093
Mattel Children's Hospital at UCLA
Los Angeles, California, United States, 90095
United States, Colorado
Children's Hospital of Denver
Denver, Colorado, United States, 80218
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Miami Children's Hospital
Miami, Florida, United States, 33155
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30342
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University in St. Louis
St. Louis, Missouri, United States, 63110
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Women and Children's Hospital of Buffalo
Buffalo, New York, United States, 14222
NYU Comprehensive Epilepsy Center, Manhattan
New York, New York, United States, 10016
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Rainbow Babies & Children's Hospital
Cleveland, Ohio, United States, 44106
Children's Hospital, Inc., PCTI
Columbus, Ohio, United States, 43205
United States, Oregon
Doernbecher Children's Hospital
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
LeBonheur Children's Medical Center
Memphis, Tennessee, United States, 38103
United States, Texas
Dallas Pediatric Neurology Associates
Dallas, Texas, United States, 75230
Cook Children's Medical Center
Ft. Worth, Texas, United States, 76104
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah/Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
United States, Virginia
Children's Hospital of The King's Daughter (Monarch Medical Research)
Norfolk, Virginia, United States, 23510
United States, Washington
Children's Hospital & Regional Medical Center
Seattle, Washington, United States, 98105-0371
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53201-1997
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
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):
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
Seizures
Brain Diseases
Central Nervous System Diseases
Epilepsy, Generalized
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Anticonvulsants
Ethosuximide
Lamotrigine
Valproic Acid
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

ClinicalTrials.gov processed this record on October 22, 2014