The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients

Kidney Transplantation Clinical Trial

Official title:

The Biomarker for CYP3A-mediated Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01699360
• Other study ID #: H3110-81072700
• Status: Recruiting
• Phase: Phase 4
• First received: September 26, 2012
• Last updated: September 30, 2012
• Start date: September 2012
• Est. completion date: December 2013

Study information

• Verified date: September 2012
• Source: Central South University
• Contact: Xi Luo, master
• Phone: +86 731 2650451
• Email: luoxicsu[@]yahoo.com.cn
• Is FDA regulated: No
• Health authority: China: National Natural Science Foundation
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the potential of endogenous cortisol and cortisone metabolism as a biomarker for immunosuppressive agents disposition in Chinese renal transplant recipients. If the blood concentrations of immunosuppressants can be predicted successfully, this new probe may take place of current drug monitoring post transplantation.

Description:

Immunosuppressive agents, including cyclosporine A, tacrolimus, and sirolimus, have been widely used to improve the outcome of organ transplantation. The need for frequent and specific monitoring of drug concentrations remains essential, since the therapeutic dosing and pharmacokinetics show great variability among recipients. However, this may be time and cost consuming. Indeed, cyclosporine A, tacrolimus, and sirolimus are all metabolized by CYP3A, consisting with the metabolic characteristic of endogenous cortisol and cortisone. Hence, the present study is designed to determine if the endogenous cortisol and cortisone metabolism can be used as an noninvasive probe for immunosuppressants pharmacokinetics in Chinese renal transplant recipients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chinese adult patients who had undergone their first renal transplantation; All patients received an immunosuppressive regimen containing immunosuppressive agents, mycophenolate mofetil, and corticosteroids; All patients had normal liver and renal function.

Exclusion Criteria:

• an acute rejection episode or infection; multiple organ transplantation; taking any other medications known to interact with immunosuppressive agents, with exception of calcium-channel blockers; abnormal findings on physical examination or laboratory tests.

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Cyclosporine A, Tacrolimus, Sirolimus

Locations

Country	Name	City	State
China	The third xiangya hospital, Central South University	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The relationship between the ratio of 6ß-hydroxycortisol and 6ß-hydroxycortisone to cortisol and cortisone in urine and pharmacokinetic parameters of immunosuppressive agents	For renal transplant recipients, blood samples are collected at 0 time point (before dosing) for the analysis of trough concentrations of immunosuppressive agents, and urine samples are gathered at 2h interval post-dose (8:00am-10:00am).; For healthy subjects, blood samples are collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24h after cyclosporine A dosing; at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72h after tacrolimus dosing; at 0, 0.33, 0.67, 1, 2, 3, 4, 5, 8, 10, 12, 16, 24, 48, 72, 96, 120h after sirolimus dosing. Urine samples are obtained for 0-10 h (8:00 am to 18:00 pm) and 10-24 h (18:00 pm to 8:00 am) post-dose. Furthermore,blood samples at 1, 4, 8, 10, 24h and urine samples for additional 24 h interval (-8:00 am to 8:00 am) before dosing are compared with those obtained after dosing to evaluate the effects of immunosuppressive agents administration on cortisol and cortisone levels and metabolism.	0-144h post-dose	No
Secondary	The relationship between plasma 6ß-hydroxylation clearance of the sum of cortisol and cortisone and pharmacokinetic parameters of immunosuppressive agents	The same as in the Primary Outcome Measure	0-144h post-dose	No