<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/NCT01724398</url>
  </required_header>
  <id_info>
    <org_study_id>UCMSC-PE</org_study_id>
    <nct_id>NCT01724398</nct_id>
  </id_info>
  <brief_title>Umbilical Cord Mesenchymal Stem Cells Transplantation Combined With Plasma Exchange for Patients With Liver Failure</brief_title>
  <official_title>Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cells Transplantation Combined With Plasma Exchange for Patients With Acute-on-Chronic Liver Failure Caused by Hepatitis B Virus (HBV)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Third Affiliated Hospital, Sun Yat-Sen University</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>
      Liver failure (LF) is a dramatic clinical syndrome with massive necrosis of liver cells.&#xD;
      Although liver transplantation provides an option to cure patients suffering with LF, lack of&#xD;
      donors, postoperative complications, especially rejection, and high cost limit its&#xD;
      application. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs)&#xD;
      the novel and promising therapeutic strategy, BM-MSCs can replace hepatocytes in injured&#xD;
      liver, and effectively rescue experimental liver failure and contribute to liver&#xD;
      regeneration. Plasma exchange (PE) can improve internal environment by removing endotoxin, it&#xD;
      helps the liver regeneration and functional recovery and make UC-MSC differentiation into&#xD;
      hepatocyte like cells, and exert immunomodulatory function. In this study, safety and&#xD;
      efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation combined&#xD;
      with plasma exchange (PE) for patients with liver failure caused by hepatitis B Virus will be&#xD;
      evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To investigate safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs)&#xD;
      transplantation combined with plasma exchange (PE) for patients with liver failure caused by&#xD;
      hepatitis B virus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <completion_date type="Anticipated">March 2015</completion_date>
  <primary_completion_date type="Anticipated">March 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival rate and time</measure>
    <time_frame>48 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improve biochemical indexes [alanine aminotransferase (ALT), albumin (ALB), total bilirubin (TBIL), prothrombin time (PT), INR and so on]</measure>
    <time_frame>24 weeks after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The clinical symptom improvement [including appetite, debilitation, abdominal distension, edema of lower limbs, et al]</measure>
    <time_frame>24 weeks after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver function evaluation using Child-Pugh score and MELD score</measure>
    <time_frame>24 weeks after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune function improvement [including Th1/Th2]</measure>
    <time_frame>24 weeks after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The occurrence of complications [including body temperature, tetter and allergy]</measure>
    <time_frame>Between 0 to 8 hours after UC-MSCs transfusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of hepatocellular carcinoma</measure>
    <time_frame>48 weeks after treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Liver Failure</condition>
  <arm_group>
    <arm_group_label>Conventional treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive conventional treatment and then be followed until the week 48 study visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional plus UC-MSC treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive conventional treatment plus a dose of UC-MSC and then be followed until the week 48 study visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional plus PE treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive conventional treatment plus plasma exchange and then be followed until the week 48 study visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional plus UC-MSC and PE therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive conventional treatment plus umbilical cord mesenchymal stem cells transplantation combined with plasma exchange. Participants will then be followed until the week 48 study visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional plus UC-MSC treatment</intervention_name>
    <description>Received conventional treatment and umbilical cord mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×105/Kg, once a week, 4 times).</description>
    <arm_group_label>Conventional plus UC-MSC treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional plus PE treatment</intervention_name>
    <description>Received conventional treatment plus 2000 milliliter plasma exchange (every 3 days, 3 times).</description>
    <arm_group_label>Conventional plus PE treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional plus UC-MSC and PE therapy</intervention_name>
    <description>Received conventional treatment plus 2000 milliliter plasma exchange (every 3 days, 3 times). Meantime taken i.v umbilical cord mesenchymal stem cells transplantation slowly for 30minutes (1×105/Kg, once a week, 4 times), the first two times is taken after plasma exchange.</description>
    <arm_group_label>Conventional plus UC-MSC and PE therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional treatment</intervention_name>
    <description>Received conventional treatment including antiviral drugs, lowering aminotransferase and jaundice medicine.</description>
    <arm_group_label>Conventional treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Acute-on-Chronic liver failure caused by hepatitis B virus&#xD;
&#xD;
          -  Model for End-Stage Liver Disease (MELD) &lt;30&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Liver failure caused by other reasons, such as autoimmune diseases, alcohol, drug and&#xD;
             so on&#xD;
&#xD;
          -  History of severe hepatic encephalopathy or variceal bleeding during the last two&#xD;
             months before enrollment&#xD;
&#xD;
          -  Severe problems in other vital organs(e.g. the heart, renal or lungs)&#xD;
&#xD;
          -  Severe bacteria infection&#xD;
&#xD;
          -  Tumor on ultrasonography, CT or MRI examination&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhi-Liang Gao, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Third Affliated Hospital of Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhi-Liang Gao, Professor</last_name>
    <phone>86-20-85252373</phone>
    <email>zhilianggao@21cn.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hong-Liang He, Master</last_name>
    <phone>86-20-85253372</phone>
    <email>hehongliang0925@sina.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Infectious Diseases, The Third Affliated Hospital of 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>Zhi-Liang Gao, Professor</last_name>
      <phone>86-20-85252373</phone>
      <email>zhilianggao@21cn.com</email>
    </contact>
    <contact_backup>
      <last_name>Hong-Liang He, Master</last_name>
      <phone>86-20-85253372</phone>
      <email>hehongliang0925@sina.com</email>
    </contact_backup>
    <investigator>
      <last_name>Zhi-Liang Gao, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2013</verification_date>
  <study_first_submitted>November 4, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>February 27, 2013</last_update_submitted>
  <last_update_submitted_qc>February 27, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 28, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Third Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Zhiliang Gao</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>mesenchymal stem cells</keyword>
  <keyword>plasma exchange</keyword>
  <keyword>liver failure</keyword>
  <keyword>hepatitis B virus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Failure</mesh_term>
    <mesh_term>Hepatic Insufficiency</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/NCT01724398
org study id: UCMSC-PE
nct id: NCT01724398
lead sponsor: 
has dmc: Yes
Liver failure (LF) is a dramatic clinical syndrome with massive necrosis of liver cells.
      Although liver transplantation provides an option to cure patients suffering with LF, lack of
      donors, postoperative complications, especially rejection, and high cost limit its
      application. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs)
      the novel and promising therapeutic strategy, BM-MSCs can replace hepatocytes in injured
      liver, and effectively rescue experimental liver failure and contribute to liver
      regeneration. Plasma exchange (PE) can improve internal environment by removing endotoxin, it
      helps the liver regeneration and functional recovery and make UC-MSC differentiation into
      hepatocyte like cells, and exert immunomodulatory function. In this study, safety and
      efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation combined
      with plasma exchange (PE) for patients with liver failure caused by hepatitis B Virus will be
      evaluated.
To investigate safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs)
      transplantation combined with plasma exchange (PE) for patients with liver failure caused by
      hepatitis B virus.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Survival rate and time
time frame: 48 weeks
measure: Improve biochemical indexes [alanine aminotransferase (ALT), albumin (ALB), total bilirubin (TBIL), prothrombin time (PT), INR and so on]
time frame: 24 weeks after treatment
measure: The clinical symptom improvement [including appetite, debilitation, abdominal distension, edema of lower limbs, et al]
time frame: 24 weeks after treatment
measure: Liver function evaluation using Child-Pugh score and MELD score
time frame: 24 weeks after treatment
measure: Immune function improvement [including Th1/Th2]
time frame: 24 weeks after treatment
measure: The occurrence of complications [including body temperature, tetter and allergy]
time frame: Between 0 to 8 hours after UC-MSCs transfusion
measure: Incidence of hepatocellular carcinoma
time frame: 48 weeks after treatment
arm group label: Conventional treatment
arm group type: Experimental
description: Participants will receive conventional treatment and then be followed until the week 48 study visit.
arm group label: Conventional plus UC-MSC treatment
arm group type: Experimental
description: Participants will receive conventional treatment plus a dose of UC-MSC and then be followed until the week 48 study visit.
arm group label: Conventional plus PE treatment
arm group type: Experimental
description: Participants will receive conventional treatment plus plasma exchange and then be followed until the week 48 study visit.
arm group label: Conventional plus UC-MSC and PE therapy
arm group type: Experimental
description: Participants will receive conventional treatment plus umbilical cord mesenchymal stem cells transplantation combined with plasma exchange. Participants will then be followed until the week 48 study visit.
intervention type: Other
intervention name: Conventional plus UC-MSC treatment
description: Received conventional treatment and umbilical cord mesenchymal stem cells transplantation by peripheral vein slowly for 30minutes. (1×105/Kg, once a week, 4 times).
arm group label: Conventional plus UC-MSC treatment
intervention type: Other
intervention name: Conventional plus PE treatment
description: Received conventional treatment plus 2000 milliliter plasma exchange (every 3 days, 3 times).
arm group label: Conventional plus PE treatment
intervention type: Other
intervention name: Conventional plus UC-MSC and PE therapy
description: Received conventional treatment plus 2000 milliliter plasma exchange (every 3 days, 3 times). Meantime taken i.v umbilical cord mesenchymal stem cells transplantation slowly for 30minutes (1×105/Kg, once a week, 4 times), the first two times is taken after plasma exchange.
arm group label: Conventional plus UC-MSC and PE therapy
intervention type: Other
intervention name: Conventional treatment
description: Received conventional treatment including antiviral drugs, lowering aminotransferase and jaundice medicine.
arm group label: Conventional treatment
criteria: 
gender: All
minimum age: 16 Years
maximum age: 65 Years
healthy volunteers: No
last name: Zhi-Liang Gao, Doctor
role: Principal Investigator
affiliation: The Third Affliated Hospital of Sun Yat-sen University
last name: Zhi-Liang Gao, Professor
phone: 86-20-85252373
email: zhilianggao@21cn.com
last name: Hong-Liang He, Master
phone: 86-20-85253372
email: hehongliang0925@sina.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Third Affiliated Hospital, Sun Yat-Sen University
investigator full name: Zhiliang Gao
investigator title: Professor
mesh term: Liver Failure
mesh term: Hepatic Insufficiency