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Genetic Drug Study of Mycophenolic Acid (CellCept) in Pediatric Kidney Transplant Patients

Phase 1
Terminated
Conditions
Kidney Transplant
Registration Number
NCT00433953
Lead Sponsor
Children's Hospital Medical Center, Cincinnati
Brief Summary

The purpose of this study is to determine how genes influence the response to mycophenolate mofetil (CellCept) in children who have had a kidney transplant. The study will look at how differences in some genes effect blood levels of mycophenolate mofetil over time in children, how often side effects occur and the way that children respond to mycophenolate mofetil.

The results may lead to better dosing based on individual needs.

Detailed Description

This is an open label, inpatient-outpatient prospective observational study to determine whether the inter-patient variability in mycophenolic acid (MPA) pharmacokinetics and exposure, adverse events and clinical response in pediatric transplant patients (ages 2-18 years) is associated with identifiable pharmacogenetic factors. Specific aims: 1.) To determine whether common polymorphic variations in the uridine diphosphate-glucuronosyltransferases (UGTs) are associated with inter-individual variability in MPA pharmacokinetics and exposure (by affecting MPA metabolism). 2.) To determine whether common polymorphic variations in the uridine diphosphate-glucuronosyltransferases (UGTs) are associated with inter-patient differences in the incidence of adverse events (by affecting the formation of the acyl-glucuronide metabolite). Enrolled subjects will have been receiving mycophenolate mofetil as part of their clinical standard of care. It is anticipated that the clinical portion of the study will last up to 4 hours at one study visit to include one pharmacogenetic blood sample and 4 pharmacokinetic blood samples collected out to 3 hours post-dose. Safety data to be collected will include standard of care physical exam and safety laboratory tests as well as data on adverse events and clinical outcomes.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
44
Inclusion Criteria
  • Male subjects and non-pregnant female subjects aged 2 to 18 years who are about to receive a kidney transplant and will be on post transplant MMF containing immunosuppressive therapy.
  • A signed and dated institutional review board (IRB) approved parental/guardian informed consent form and an IRB approved child assent form if applicable.
  • Subjects with stable kidney allografts who are on a stable regimen of MMF (with tacrolimus and steroids)
  • May have clinically important abnormalities on clinical and /or laboratory evaluations, only as these abnormalities relate to an underlying condition as determined by the principal investigator.
Exclusion Criteria
  • Children receiving cyclosporine therapy that may interact with MPA entero-hepatic recycling.
  • Any medical condition(active or chronic) or prior surgery that may interfere with the pharmacokinetics of MMF as determined by the principal investigator.
  • Concomitant medication that may interfere with the pharmacokinetics of MMF as determined by the principal investigator.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Drug measurement of MPA, MPA-G and acyl-MPA-GDay 1
The following outcome measures will be performed at the study visit after the patient is on a steady state dose of mycophenolate mofetil:Day 1
Genomic DNA extraction using standard procedures. Patients will be genotyped for the UGT2B7, UGT1A8, UGT1A9 polymorphism.Day 1
Secondary Outcome Measures
NameTimeMethod
Physical ExamDay 1
Safety Laboratory testsDay 1
Dietary MonitoringDay 1
Concomitant medications and mycophenolate mofetil drug diaryDay 1
Adverse Event ReportingDay 1

Trial Locations

Locations (1)

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

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