Pathogenesis of Adverse Drug Reactions

Seizures Clinical Trial

Official title:

The Role of Drug Metabolizing Enzymes in the Pathogenesis Adverse Drug Reactions in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00224952
• Other study ID #: PPRU 10606
• Secondary ID: NIH Grant HD0442
• Status: Completed
• Phase: N/A
• First received: September 21, 2005
• Last updated: August 11, 2017
• Start date: July 2002
• Est. completion date: March 2010

Study information

• Verified date: August 2017
• Source: Children's Mercy Hospital Kansas City
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 274
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 16 Years

Eligibility

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:

Related Conditions & MeSH terms

• Drug-Related Side Effects and Adverse Reactions
• Seizures

Intervention

Other:
• No intervention; Urine Collection
Urine collected from children receiving carbamazepine or valproic acid as part of their clinical management

Locations

Country	Name	City	State
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Primary Children's Hospital, Pediatric Neurology	Salt Lake City	Utah

Sponsors (4)

Lead Sponsor	Collaborator
Children's Mercy Hospital Kansas City	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Louisville, University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Drug (Valproic Acid or Carbamazepine) Metabolite Profiles in Urine	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).	urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years
Secondary	Age-related Changes in Bioactivation	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.	urine samples (overnight collections) collected longitudinally through study completion for time frame ranging from 2-5 years

External Links

•   Pediatric Pharmacology Research Units Website