<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01699360</url>
  </required_header>
  <id_info>
    <org_study_id>H3110-81072700</org_study_id>
    <nct_id>NCT01699360</nct_id>
  </id_info>
  <brief_title>The Biomarker for Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients</brief_title>
  <official_title>The Biomarker for CYP3A-mediated Immunosuppressive Agents Metabolism in Chinese Renal Transplant Recipients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central South University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central South University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate the potential of endogenous cortisol and cortisone&#xD;
      metabolism as a biomarker for immunosuppressive agents disposition in Chinese renal&#xD;
      transplant recipients. If the blood concentrations of immunosuppressants can be predicted&#xD;
      successfully, this new probe may take place of current drug monitoring post transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Immunosuppressive agents, including cyclosporine A, tacrolimus, and sirolimus, have been&#xD;
      widely used to improve the outcome of organ transplantation. The need for frequent and&#xD;
      specific monitoring of drug concentrations remains essential, since the therapeutic dosing&#xD;
      and pharmacokinetics show great variability among recipients. However, this may be time and&#xD;
      cost consuming. Indeed, cyclosporine A, tacrolimus, and sirolimus are all metabolized by&#xD;
      CYP3A, consisting with the metabolic characteristic of endogenous cortisol and cortisone.&#xD;
      Hence, the present study is designed to determine if the endogenous cortisol and cortisone&#xD;
      metabolism can be used as an noninvasive probe for immunosuppressants pharmacokinetics in&#xD;
      Chinese renal transplant recipients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">December 2013</completion_date>
  <primary_completion_date type="Anticipated">September 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The relationship between the ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone in urine and pharmacokinetic parameters of immunosuppressive agents</measure>
    <time_frame>0-144h post-dose</time_frame>
    <description>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).&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The relationship between plasma 6β-hydroxylation clearance of the sum of cortisol and cortisone and pharmacokinetic parameters of immunosuppressive agents</measure>
    <time_frame>0-144h post-dose</time_frame>
    <description>The same as in the Primary Outcome Measure</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Kidney Transplantation</condition>
  <arm_group>
    <arm_group_label>Cyclosporine A, Tacrolimus, Sirolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cyclosporine A：soft capsule,2-6mg/kg/d, the same twice daily dose at least five days.&#xD;
Tacrolimus:capsule,0.15-0.3mg/kg/d, the same twice daily dose at least five days.&#xD;
Sirolimus:tablet,2mg/d, once a day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclosporine A, Tacrolimus, Sirolimus</intervention_name>
    <arm_group_label>Cyclosporine A, Tacrolimus, Sirolimus</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chinese adult patients who had undergone their first renal transplantation； All&#xD;
             patients received an immunosuppressive regimen containing immunosuppressive agents,&#xD;
             mycophenolate mofetil, and corticosteroids; All patients had normal liver and renal&#xD;
             function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  an acute rejection episode or infection; multiple organ transplantation; taking any&#xD;
             other medications known to interact with immunosuppressive agents, with exception of&#xD;
             calcium-channel blockers; abnormal findings on physical examination or laboratory&#xD;
             tests.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zeneng cheng, doctor</last_name>
    <role>Study Director</role>
    <affiliation>Central South University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xi Luo, master</last_name>
    <phone>+86 731 2650451</phone>
    <email>luoxicsu@yahoo.com.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The third xiangya hospital, Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410013</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Xi Luo, master</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>September 30, 2012</last_update_submitted>
  <last_update_submitted_qc>September 30, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 3, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Central South University</investigator_affiliation>
    <investigator_full_name>Xi Luo</investigator_full_name>
    <investigator_title>clinical research assistant</investigator_title>
  </responsible_party>
  <keyword>Kidney Transplantation</keyword>
  <keyword>Immunosuppressive Agents</keyword>
  <keyword>Hydrocortisone</keyword>
  <keyword>Cortisone</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclosporine</mesh_term>
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
    <mesh_term>Cyclosporins</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01699360
org study id: H3110-81072700
nct id: NCT01699360
lead sponsor: 
has dmc: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 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
description: 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.
measure: 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
description: The same as in the Primary Outcome Measure
arm group label: Cyclosporine A, Tacrolimus, Sirolimus
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: Cyclosporine A, Tacrolimus, Sirolimus
arm group label: Cyclosporine A, Tacrolimus, Sirolimus
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Zeneng cheng, doctor
role: Study Director
affiliation: Central South University
last name: Xi Luo, master
phone: +86 731 2650451
email: luoxicsu@yahoo.com.cn
facility: 
status: Recruiting
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Central South University
investigator full name: Xi Luo
investigator title: clinical research assistant
mesh term: Cyclosporine
mesh term: Sirolimus
mesh term: Tacrolimus
mesh term: Cyclosporins