Influence of Genes on Sirolimus Metabolism in Patients Wi... | NCT00352547

Studies
Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation

NCT00352547

Sponsor

National Institutes of Health Clinical Center (CC)

Status

Completed

Last Update Posted

Oct 6, 2017Actual

Enrollment

93Actual

Phase

Not provided

Conditions

Renal Transplant

Interventions

Not provided

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

ID	Type	Description	Link
04-CC-0184

Status Module

Record Verification Date

Dec 2, 2013

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

May 21, 2004

Primary Completion Date

Not provided

Completion Date

Dec 2, 2013

First Submitted Date

Jul 13, 2006

First Submission Date that Met QC Criteria

Jul 13, 2006

First Posted Date

Jul 14, 2006Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 5, 2017

Last Update Posted Date

Oct 6, 2017Actual

Sponsor/Collaborators Module

Responsible Party, by Official Title

Not provided

Lead Sponsor

National Institutes of Health Clinical Center (CC)NIH

Collaborators

Not provided

Description Module

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.

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.

Design Module

Study Type

Observational

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not provided

Interventional Study Design

No data available

No data is available for this block.

Biospecimen

No data available

No data is available for this block.

Enrollment

93Actual

Eligibility Module

Eligibility 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.

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

Not provided

Maximum Age

Not provided

Standard Ages

ChildAdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Scott R Penzak, Pharm.D.	National Institutes of Health Clinical Center (CC)	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike		Bethesda	Maryland	20892	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
1385058	Background	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.
9129559	Background	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.