Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation
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First Received Date ICMJE | July 13, 2006 | ||||
Last Updated Date | May 31, 2012 | ||||
Start Date ICMJE | May 2004 | ||||
Primary Completion Date | |||||
Current Primary Outcome Measures ICMJE | |||||
Original Primary Outcome Measures ICMJE |
Changes in Verbal and Nonverbal short term memory. | ||||
Change History | Complete list of historical versions of study NCT00352547 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures ICMJE | |||||
Original Secondary Outcome Measures ICMJE | |||||
Current Other Outcome Measures ICMJE | |||||
Original Other Outcome Measures ICMJE | |||||
Descriptive Information | |||||
Brief Title ICMJE | Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation | ||||
Official Title ICMJE | Influence of MDR-1 CYP3A4 and CYP3A5 Genotypes/Haplotypes on Sirolimus Pharmacokinetics and Pharmacodynamics in Patients With Renal Transplantation | ||||
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 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. |
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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. |
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Study Type ICMJE | Observational | ||||
Study Design ICMJE | |||||
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Study Population | |||||
Condition ICMJE | Renal Transplant | ||||
Intervention ICMJE | |||||
Study Group/Cohort (s) | |||||
Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Enrollment ICMJE | 93 | ||||
Completion Date | |||||
Primary Completion Date | |||||
Eligibility Criteria ICMJE |
Patients who meet the following criteria will be included in the study:
EXCLUSION CRITERIA: Patients with clearly documented non-compliance to medications including sirolimus will be excluded from the study. |
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Gender | Both | ||||
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Accepts Healthy Volunteers | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Location Countries ICMJE | United States | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT00352547 | ||||
Other Study ID Numbers ICMJE | 040184, 04-CC-0184 | ||||
Has Data Monitoring Committee | |||||
Responsible Party | |||||
Study Sponsor ICMJE | National Institutes of Health Clinical Center (CC) | ||||
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Information Provided By | National Institutes of Health Clinical Center (CC) | ||||
Verification Date | December 2011 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |