The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients

Sponsor

Central South University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01699360

Collaborator

(none)

600

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: Cyclosporine A, Tacrolimus, Sirolimus	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2012

Anticipated Primary Completion Date :

Sep 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclosporine A, Tacrolimus, Sirolimus Cyclosporine A：soft capsule,2-6mg/kg/d, the same twice daily dose at least five days. Tacrolimus:capsule,0.15-0.3mg/kg/d, the same twice daily dose at least five days. Sirolimus:tablet,2mg/d, once a day.	Drug: Cyclosporine A, Tacrolimus, Sirolimus

Arm

Intervention/Treatment

Experimental: Cyclosporine A, Tacrolimus, Sirolimus

Cyclosporine A：soft capsule,2-6mg/kg/d, the same twice daily dose at least five days. Tacrolimus:capsule,0.15-0.3mg/kg/d, the same twice daily dose at least five days. Sirolimus:tablet,2mg/d, once a day.

Drug: Cyclosporine A, Tacrolimus, Sirolimus

Outcome Measures

Primary Outcome Measures

The relationship between the ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone in urine and pharmacokinetic parameters of immunosuppressive agents [0-144h post-dose]
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.

Secondary Outcome Measures

The relationship between plasma 6β-hydroxylation clearance of the sum of cortisol and cortisone and pharmacokinetic parameters of immunosuppressive agents [0-144h post-dose]
The same as in the Primary Outcome Measure

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.