The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2012 by Central South University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Xi Luo, Central South University
ClinicalTrials.gov Identifier:
NCT01699360
First received: September 26, 2012
Last updated: September 30, 2012
Last verified: September 2012
  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

Resource links provided by NLM:


Further study details as provided by Central South University:

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 [ 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.



Secondary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01699360

Contacts
Contact: Xi Luo, master +86 731 2650451 luoxicsu@yahoo.com.cn

Locations
China, Hunan
The third xiangya hospital, Central South University Recruiting
Changsha, Hunan, China, 410013
Principal Investigator: Xi Luo, master         
Sponsors and Collaborators
Central South University
Investigators
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:
Cyclosporine
Cyclosporins
Everolimus
Immunosuppressive Agents
Sirolimus
Tacrolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014