Clinical trial NCT00224952: Pathogenesis of Adverse Drug Reactions
Official title: The Role of Drug Metabolizing Enzymes in the Pathogenesis Adverse Drug Reactions in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Seizures
Keywords: seizures
Epilepsy
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of Utah
name: University of Louisville
First posted: 2005-09-23
Enrollment: 274
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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 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

Primary outcomes:
measure: Drug (Valproic Acid or Carbamazepine) Metabolite Profiles in Urine
timeFrame: urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years
Secondary outcomes:
measure: Age-related Changes in Bioactivation
timeFrame: urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Salt Lake City
country: United States
facility: Primary Children's Hospital, Pediatric Neurology
state: Utah
Study officials:
affiliation: Children's Mercy Hospital Kansas City
name: J. Steven Leeder, Pharm.D., Ph.D.,
role: PRINCIPAL_INVESTIGATOR
References: