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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
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Utah
University of Louisville
Information provided by (Responsible Party):
Steve Leeder, Children's Mercy Hospital Kansas City

Tracking Information
First Submitted Date September 21, 2005
First Posted Date September 23, 2005
Results First Submitted Date April 18, 2017
Results First Posted Date August 14, 2017
Last Update Posted Date August 14, 2017
Study Start Date July 2002
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 11, 2017)		 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).
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00224952 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: August 11, 2017)		 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.
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Pathogenesis of Adverse Drug Reactions
Official Title The Role of Drug Metabolizing Enzymes in the Pathogenesis Adverse Drug Reactions in Children
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.
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Urine DNA (source: blood or saliva)
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
Condition Seizures
Intervention 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
Study Groups/Cohorts Patients receiving Carbamazepine or Valproic Acid
Intervention: Other: No intervention; Urine Collection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: August 11, 2017)		 274
Original Enrollment
 (submitted: September 21, 2005)		 120
Actual Study Completion Date March 2010
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 1 Year to 16 Years   (Child)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00224952
Other Study ID Numbers PPRU 10606
NIH Grant HD044239
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Steve Leeder, Children's Mercy Hospital Kansas City
Study Sponsor Children's Mercy Hospital Kansas City
Collaborators
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • University of Utah
  • University of Louisville
Investigators
Principal Investigator: J. Steven Leeder, Pharm.D., Ph.D., Children's Mercy Hospital Kansas City
PRS Account Children's Mercy Hospital Kansas City
Verification Date August 2017