Influence of Genes on Sirolimus Metabolism in Patients With Kidney Transplantation

NCT00352547 | Completed

• 2 other identifiers: 04018404-CC-0184
• Study Type: observational
• Target: 93
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Transplant

Keywords

Immunosuppresant; Genetic Polymorphism; Drug Metabolism; Pharmacogenetics; Rapamycin

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 1385058 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.

  PMID: 9129559 BACKGROUND

• 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.

  PMID: 10770413 BACKGROUND

Study Officials

• Scott R Penzak, Pharm.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 13, 2006
• First Posted: July 14, 2006
• Study Start: May 21, 2004
• Study Completion: December 2, 2013
• Last Updated: October 6, 2017

Record last verified: 2013-12-02

Locations

US (1)