Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00352547
First received: July 13, 2006
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

This study will evaluate the effects of certain genes (MDR-1, CYP3A4, and CYP3A5) on metabolism of the drug sirolimus, an immune-suppressing drug given to transplant recipients to prevent organ rejection. Individual differences in metabolism and excretion of sirolimus affect the patient's response to treatment.

Patients who have undergone kidney transplantation at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Transplant Branch and have received sirolimus treatment will be enrolled in this study.

DNA (genetic material) will be extracted from blood samples collected from transplant recipients to determine their MDR-1, CYP3A4, and CYP3A5 genotypes. Patient demographic information and data on sirolimus metabolism and excretion will be collected from the medical information system, NIDDK transplant database, and the patients' medical records. The data will be compared among patients with different genotypes (genetic constitution of an individual) and haplotypes (set of genes that code for different proteins but are inherited as a unit) to determine the effect of these gene variations on sirolimus metabolism.

Information from this study may be applied to developing better dosing strategies, and thus, treatment outcomes for transplant patients receiving sirolimus.


Condition
Renal Transplant

Study Type: Observational
Official Title: Influence of MDR-1 CYP3A4 and CYP3A5 Genotypes/Haplotypes on Sirolimus Pharmacokinetics and Pharmacodynamics in Patients With Renal Transplantation

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 93
Study Start Date: May 2004
Estimated Study Completion Date: December 2013
Detailed Description:

The immunosuppressant sirolimus is a substrate for the drug efflux pump p-glycoprotein

(Pgp) and the hepatic and intestinal drug metabolizing enzyme cytochrome P450 3A4/5

(CYP3A4/5). Single nucleotide polymorphisms (SNPs) in the multi-drug resistance (MDR)-1

gene which encodes for the Pgp, CYP3A4, and CYP3A5 genes have been shown to be associated with altered metabolism of various drugs including the immunosuppressants cyclosporine and tacrolimus. This protocol will evaluate the effects of MDR-1, CYP3A4, and CYP3A5 gentotypes/haplotypes on the pharmacokinetics and pharmacodynamics of sirolimus in patients with renal transplantation. All patients who had kidney transplantation at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Transplant Branch, participated in one of the NIDDK therapeutic protocols, and have received sirolimus will be enrolled in this study. Selected MDR-1, CYP3A4, and CYP3A5 SNPs will be determined by polymerase chain reaction based methods using existing patient blood samples. Demographic, pharmacokinetic, and pharmacodynamic data will be collected from the medical information system, NIDDK transplant database, and medical records of these patients. Population pharmacokinetic parameters and pharmacodynamic measurements will then be compared among patients with different MDR-1, CYP3A4, and CYP3A5 genotypes/haplotypes. Results from this study will help to understand the effects of pharmacogenetics on sirolimus pharmacokinetics and pharmacodynamics, and will provide information for rationalizing sirolimus dosing in patients with renal transplantation.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients who meet the following criteria will be included in the study:

  • Underwent kidney transplantation at the NIDDK Transplant Branch; and
  • Participated in one of the NIDDK therapeutic protocols, and
  • Have received or switched to sirolimus

EXCLUSION CRITERIA:

Patients with clearly documented non-compliance to medications including sirolimus will be excluded from the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352547

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Scott R Penzak, Pharm.D. National Institutes of Health Clinical Center (CC)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00352547     History of Changes
Other Study ID Numbers: 040184, 04-CC-0184
Study First Received: July 13, 2006
Last Updated: December 3, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immunosuppresant
Genetic Polymorphism
Drug Metabolism
Pharmacogenetics
Rapamycin

ClinicalTrials.gov processed this record on November 20, 2014