<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/NCT02223897</url>
  </required_header>
  <id_info>
    <org_study_id>2014006</org_study_id>
    <nct_id>NCT02223897</nct_id>
  </id_info>
  <brief_title>Mesenchymal Stem Cells Transplantation for Ischemic-type Biliary Lesions</brief_title>
  <official_title>Umbilical Cord Mesenchymal Stem Cells Transplantation for Treatment of Patients With Ischemic-type Biliary Lesions After Liver Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yang Yang</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Third Affiliated Hospital, Sun Yat-Sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ischemic-type biliary lesions (ITBLs) are a major cause of graft loss and mortality after&#xD;
      orthotopic liver transplantation (OLT). For now, there are still lacking effective treatment&#xD;
      for ITBLs. The purpose of this study is to confirm whether human umbilical cord mesenchymal&#xD;
      stem cells are effective in the treatment,or prevention of Ischemic-type Biliary Lesions&#xD;
      after liver transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Advances in organ preservation techniques, immunosuppressive regimens, and surgical&#xD;
      techniques have resulted in reduced rates of infection, acute rejection and vascular&#xD;
      complications after orthotopic liver transplantation (OLT). However, ischemic-type biliary&#xD;
      lesions (ITBLs) are still one of the most serious complications after OLT, with a usual&#xD;
      reported incidence of 5-15%, and an incidence of up to 26% in some studies. 46% patients with&#xD;
      ITBLs require re-transplantation after 2 years of OLT.&#xD;
&#xD;
      Mesenchymal stem cells (MSCs),a kind of pluripotent stem cells,can differentiate into&#xD;
      vascular endothelial cells, which participate in angiogenesis in ischemic tissue. MSCs can&#xD;
      also stimulate the proliferation and migration of mature endothelial cells via&#xD;
      paracrine.Furthermore, MSCs secret a variety of cytokines and growth factors, such as&#xD;
      vascular endothelial growth factor, human basic fibroblast growth factor, hepatocyte growth&#xD;
      factor, interleukin-1 and interleukin-8, etc., which also induce angiogenesis.&#xD;
&#xD;
      Participants in the study will be randomly assigned to one of two treatment arms:&#xD;
&#xD;
        -  Arm A: Participants will receive 6 months of standard regular treatment for ITBLs plus&#xD;
           huc-MSCs treatment.&#xD;
&#xD;
        -  Arm B: Participants will receive 6 months of standard regular treatment for ITBLs plus&#xD;
           placebo.&#xD;
&#xD;
      huc-MSCs will be prepared according to standard procedures and is collected in plastic bags&#xD;
      containing anti coagulant. MSCs are given via i.v. After huc-MSCs transfusion, patients are&#xD;
      followed up once per week(in the first months,&lt;1M),once per 2 week(1-3M)and once per&#xD;
      month(3-6M), and the evaluation of liver function and biliary blood supply was performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">June 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of ITBLs</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in biliary enzymology</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biliary blood supply</measure>
    <time_frame>18 months</time_frame>
    <description>Biliary blood supply indicated by contrast-enhanced ultrasound.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>life quality</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">66</enrollment>
  <condition>Ischemic-type Biliary Lesions</condition>
  <arm_group>
    <arm_group_label>Conventional treatment, huc-MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Received conventional treatment and huc-MSCs once per week for the first month and once per month for 6 months(9 times in total), at a dose of 1×106 huc-MSCs/kg body weight.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional plus placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Received conventional treatment and 50 ml saline once per week for the first month and once per month for 6 months(9 times in total).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>huc-MSCs</intervention_name>
    <description>Received conventional treatment and huc-MSCs once per week for the first month and once per month for 6 months(9 times in total), at a dose of 1×106 huc-MSCs/kg body weight.</description>
    <arm_group_label>Conventional treatment, huc-MSCs</arm_group_label>
    <other_name>Umbilical Cord-Derived Mesenchymal Stem Cells</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Received conventional treatment and 50 ml saline solution once per week for the first month and once per month for 6 months(9 times in total).</description>
    <arm_group_label>Conventional plus placebo</arm_group_label>
    <other_name>saline solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  benign end-stage liver disease patients with liver transplantation.&#xD;
&#xD;
          -  ages of 18 and 60 years.&#xD;
&#xD;
          -  first liver transplant.&#xD;
&#xD;
          -  gamma-glutamyltransferase &gt; 300 U/L for 2 weeks, and there was no or low enhancement&#xD;
             of the wall of the hilar bile duct in arterial phase via contrast-enhanced&#xD;
             ultrasonography.&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  second or combined organ transplant recipient.&#xD;
&#xD;
          -  vital organs failure (Cardiac, Renal or Respiratory, et al).&#xD;
&#xD;
          -  clinically active bacterial, fungal, viral or parasitic infection.&#xD;
&#xD;
          -  other candidates who are judged to be not applicable to this study by investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yang Yang, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Third Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yang yang, MD</last_name>
    <email>yysysu@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Third Affiliated Hospital, Sun Yat-Sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510630</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yang Yang, PHD</last_name>
      <email>yysysu@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Yingcai Zhang</last_name>
      <email>76207884@qq.com</email>
    </contact_backup>
    <investigator>
      <last_name>Yang Yang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>August 21, 2014</last_update_submitted>
  <last_update_submitted_qc>August 21, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 22, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Third Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Yang Yang</investigator_full_name>
    <investigator_title>Department of Transplantation</investigator_title>
  </responsible_party>
  <keyword>Liver transplantation</keyword>
  <keyword>Biliary complication</keyword>
  <keyword>mesenchymal stem cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ischemia</mesh_term>
  </condition_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/NCT02223897
org study id: 2014006
nct id: NCT02223897
lead sponsor: 
has dmc: Yes
Ischemic-type biliary lesions (ITBLs) are a major cause of graft loss and mortality after
      orthotopic liver transplantation (OLT). For now, there are still lacking effective treatment
      for ITBLs. The purpose of this study is to confirm whether human umbilical cord mesenchymal
      stem cells are effective in the treatment,or prevention of Ischemic-type Biliary Lesions
      after liver transplantation.
Advances in organ preservation techniques, immunosuppressive regimens, and surgical
      techniques have resulted in reduced rates of infection, acute rejection and vascular
      complications after orthotopic liver transplantation (OLT). However, ischemic-type biliary
      lesions (ITBLs) are still one of the most serious complications after OLT, with a usual
      reported incidence of 5-15%, and an incidence of up to 26% in some studies. 46% patients with
      ITBLs require re-transplantation after 2 years of OLT.

      Mesenchymal stem cells (MSCs),a kind of pluripotent stem cells,can differentiate into
      vascular endothelial cells, which participate in angiogenesis in ischemic tissue. MSCs can
      also stimulate the proliferation and migration of mature endothelial cells via
      paracrine.Furthermore, MSCs secret a variety of cytokines and growth factors, such as
      vascular endothelial growth factor, human basic fibroblast growth factor, hepatocyte growth
      factor, interleukin-1 and interleukin-8, etc., which also induce angiogenesis.

      Participants in the study will be randomly assigned to one of two treatment arms:

        -  Arm A: Participants will receive 6 months of standard regular treatment for ITBLs plus
           huc-MSCs treatment.

        -  Arm B: Participants will receive 6 months of standard regular treatment for ITBLs plus
           placebo.

      huc-MSCs will be prepared according to standard procedures and is collected in plastic bags
      containing anti coagulant. MSCs are given via i.v. After huc-MSCs transfusion, patients are
      followed up once per week(in the first months,<1M),once per 2 week(1-3M)and once per
      month(3-6M), and the evaluation of liver function and biliary blood supply was performed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: The incidence of ITBLs
time frame: 18 months
measure: Changes in biliary enzymology
time frame: 18 months
measure: Biliary blood supply
time frame: 18 months
description: Biliary blood supply indicated by contrast-enhanced ultrasound.
measure: life quality
time frame: 18 months
arm group label: Conventional treatment, huc-MSCs
arm group type: Experimental
description: Received conventional treatment and huc-MSCs once per week for the first month and once per month for 6 months(9 times in total), at a dose of 1×106 huc-MSCs/kg body weight.
arm group label: Conventional plus placebo
arm group type: Placebo Comparator
description: Received conventional treatment and 50 ml saline once per week for the first month and once per month for 6 months(9 times in total).
intervention type: Drug
intervention name: huc-MSCs
description: Received conventional treatment and huc-MSCs once per week for the first month and once per month for 6 months(9 times in total), at a dose of 1×106 huc-MSCs/kg body weight.
arm group label: Conventional treatment, huc-MSCs
other name: Umbilical Cord-Derived Mesenchymal Stem Cells
intervention type: Drug
intervention name: Placebo
description: Received conventional treatment and 50 ml saline solution once per week for the first month and once per month for 6 months(9 times in total).
arm group label: Conventional plus placebo
other name: saline solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Yang Yang, MD
role: Study Chair
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
last name: Yang yang, MD
email: yysysu@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Third Affiliated Hospital, Sun Yat-Sen University
investigator full name: Yang Yang
investigator title: Department of Transplantation
mesh term: Ischemia