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Pathogenesis of Adverse Drug Reactions
The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2008 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).   Recruitment status was  Active, not recruiting

First Received on September 21, 2005.   Last Updated on December 15, 2008   History of Changes
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators: University of Utah
University of Louisville
Information provided by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00224952
  Purpose

The purpose of the study is to examine the individual metabolic profiles of pediatric patients receiving carbamazepine or valproate therapy, in an attempt to determine identities of the reactive metabolites or, alternatively, the identities of those metabolites that serve as potential precursors to reactive species.


Condition Intervention
Seizures
Other: No intervention; Urine Collection

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Role of Drug Metabolizing Enzymes in the Pathogenesis Adverse Drug Reactions in Children

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Biospecimen Retention:   Samples With DNA

Urine DNA (source: blood or saliva)


Estimated Enrollment: 120
Study Start Date: July 2002
Groups/Cohorts Assigned Interventions
1 Other: No intervention; Urine Collection
Urine collected from children receiving carbamazepine or valproic acid as part of their clinical management
Other Names:
  • carbamazepine: Tegretol
  • valproic acid: Depakote
2

Detailed Description:

Adverse drug reactions can be broadly defined as any undesirable response associated with therapeutic drug use. A simple and clinically useful classification is to divide adverse events into those that are dose-dependent and largely predictable from the known pharmacologic properties of the compound in question, and those that are dependent on characteristics unique to susceptible individuals, or idiosyncratic in nature.

The long term objective of this research is to characterize the mechanisms responsible for the pathogenesis of idiosyncratic hypersensitivity reactions in children, particularly those involving carbamazepine and other aromatic anticonvulsants.

The study is divided into two phases. Phase 1 of the study involves collecting urine from 50 patients taking CBZ therapeutically. Participants will be asked to provide a spot urine sample during routine health visits. The urine will be analyzed for the presence of CBZ and its metabolites. In Phase 2 of the study, urine will be collected from patients taking either CBZ or VPA therapeutically. If blood samples are drawn from these patients for medical purposes not related to this study the residual blood sample will be recovered before it is discarded for use in genotyping analysis. Participants will be asked to provide a urine sample covering one complete dosing interval of CBZ or VPA (preferably overnight). Patients will also be followed longitudinally, with urine collections at each clinic visit over at least a two year period.

  Eligibility

Ages Eligible for Study:   1 Year to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Pediatric patients of both genders between 1 and 16 years of age receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy or polytherapy

Criteria

Inclusion Criteria:

  • Pediatric patients of both genders between 1 and 16 years of age receiving CBZ or VPA mono-therapy will be recruited for this study. Additionally, for those patients who are receiving drugs other than CBZ or VPA to control their seizures, if CBZ or VPA are subsequently added to their treatment regimen, then these patients will also be recruited for this study.

Exclusion Criteria:

  • None
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00224952

Locations
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Utah
Primary Children's Hospital, Pediatric Neurology
Salt Lake City, Utah, United States, 84113
Sponsors and Collaborators
University of Utah
University of Louisville
Investigators
Principal Investigator: J. Steven Leeder, Pharm.D., Ph.D., Children's Mercy Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: LEEDER, James Steven, Children's Mercy Hospitals and Clinics
ClinicalTrials.gov Identifier: NCT00224952     History of Changes
Other Study ID Numbers: PPRU 10606, NIH Grant HD044239
Study First Received: September 21, 2005
Last Updated: December 15, 2008
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
seizures
Epilepsy

Additional relevant MeSH terms:
Seizures
Drug Toxicity
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Poisoning
Substance-Related Disorders
Valproic Acid
Carbamazepine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012