Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation
NCT ID: NCT00352547
Last Updated: 2017-10-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
93 participants
OBSERVATIONAL
2004-05-21
2013-12-02
Brief Summary
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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.
Detailed Description
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(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.
Conditions
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Eligibility Criteria
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Inclusion Criteria
* 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
ALL
No
Sponsors
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National Institutes of Health Clinical Center (CC)
NIH
Principal Investigators
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Scott R Penzak, Pharm.D.
Role: PRINCIPAL_INVESTIGATOR
National Institutes of Health Clinical Center (CC)
Locations
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Countries
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References
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Sattler M, Guengerich FP, Yun CH, Christians U, Sewing KF. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos. 1992 Sep-Oct;20(5):753-61.
Ferron GM, Mishina EV, Zimmerman JJ, Jusko WJ. Population pharmacokinetics of sirolimus in kidney transplant patients. Clin Pharmacol Ther. 1997 Apr;61(4):416-28. doi: 10.1016/S0009-9236(97)90192-2.
Kahan BD, Napoli KL, Kelly PA, Podbielski J, Hussein I, Urbauer DL, Katz SH, Van Buren CT. Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity. Clin Transplant. 2000 Apr;14(2):97-109. doi: 10.1034/j.1399-0012.2000.140201.x.
Other Identifiers
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04-CC-0184
Identifier Type: -
Identifier Source: secondary_id
040184
Identifier Type: -
Identifier Source: org_study_id