The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Kidney Transplantation |
Drug: Cyclosporine A, Tacrolimus, Sirolimus |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | The Biomarker for CYP3A-mediated Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients |
- The relationship between the ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone in urine and pharmacokinetic parameters of immunosuppressive agents [ Time Frame: 0-144h post-dose ] [ Designated as safety issue: No ]
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.
- The relationship between plasma 6β-hydroxylation clearance of the sum of cortisol and cortisone and pharmacokinetic parameters of immunosuppressive agents [ Time Frame: 0-144h post-dose ] [ Designated as safety issue: No ]The same as in the Primary Outcome Measure
| Estimated Enrollment: | 600 |
| Study Start Date: | September 2012 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| 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.
Contacts and Locations| Contact: Xi Luo, master | +86 731 2650451 | luoxicsu@yahoo.com.cn |
| China, Hunan | |
| The third xiangya hospital, Central South University | Recruiting |
| Changsha, Hunan, China, 410013 | |
| Principal Investigator: Xi Luo, master | |
| Study Director: | Zeneng cheng, doctor | Central South University |
More Information
No publications provided
| Responsible Party: | Xi Luo, clinical research assistant, Central South University |
| ClinicalTrials.gov Identifier: | NCT01699360 History of Changes |
| Other Study ID Numbers: | H3110-81072700 |
| Study First Received: | September 26, 2012 |
| Last Updated: | September 30, 2012 |
| Health Authority: | China: National Natural Science Foundation |
Keywords provided by Central South University:
|
Kidney Transplantation Immunosuppressive Agents Hydrocortisone Cortisone |
Additional relevant MeSH terms:
|
Cyclosporins Cyclosporine Immunosuppressive Agents Sirolimus Everolimus Tacrolimus Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Immunologic Factors |
Physiological Effects of Drugs Antifungal Agents Anti-Infective Agents Therapeutic Uses Dermatologic Agents Antirheumatic Agents Antibiotics, Antineoplastic Antineoplastic Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 19, 2013