Pathogenesis of Adverse Drug Reactions
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00224952|
Recruitment Status : Completed
First Posted : September 23, 2005
Results First Posted : August 14, 2017
Last Update Posted : August 14, 2017
|Condition or disease||Intervention/treatment|
|Seizures||Other: No intervention; Urine Collection|
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.
|Study Type :||Observational|
|Actual Enrollment :||274 participants|
|Official Title:||The Role of Drug Metabolizing Enzymes in the Pathogenesis Adverse Drug Reactions in Children|
|Study Start Date :||July 2002|
|Actual Primary Completion Date :||March 2010|
|Actual Study Completion Date :||March 2010|
|Patients receiving Carbamazepine or Valproic Acid||
Other: No intervention; Urine Collection
Urine collected from children receiving carbamazepine or valproic acid as part of their clinical management
- Drug (Valproic Acid or Carbamazepine) Metabolite Profiles in Urine [ Time Frame: urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years ]1. To examine the individual metabolic profiles of pediatric patients receiving carbamazepine or valproate therapy, in an attempt to determine the identities of the reactive metabolites or, alternatively, the identities of those metabolites that serve as potential precursors to reactive species (e.g., through conjugation with detoxifying compounds such as glutathione).
- Age-related Changes in Bioactivation [ Time Frame: urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years ]2. To determine if age-related differences exist regarding the ability of pediatric patients to bioactivate carbamazepine or valproate to reactive metabolites. Data provided below reflect the slope of the least squares regression.
Biospecimen Retention: Samples With DNA
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): NCT00224952
|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|
|Principal Investigator:||J. Steven Leeder, Pharm.D., Ph.D.,||Children's Mercy Hospital Kansas City|