Ignite Creation Date:
2024-05-05 @ 4:58 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00352547
Status:
COMPLETED
Last Update Posted:
2017-10-06
First Post:
2006-07-13
Brief Title:
Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Influence of MDR-1 CYP3A4 and CYP3A5 GenotypesHaplotypes on Sirolimus Pharmacokinetics and Pharmacodynamics in Patients With Renal Transplantation
Status:
COMPLETED
Status Verified Date:
2013-12-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 patients 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
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:
The immunosuppressant sirolimus is a substrate for the drug efflux pump p-glycoprotein
Pgp and the hepatic and intestinal drug metabolizing enzyme cytochrome P450 3A45
CYP3A45 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 gentotypeshaplotypes 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 genotypeshaplotypes 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
Pgp and the hepatic and intestinal drug metabolizing enzyme cytochrome P450 3A45
CYP3A45 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 gentotypeshaplotypes 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 genotypeshaplotypes 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-CC-0184 | None | None | None |