<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/NCT01662973</url>
  </required_header>
  <id_info>
    <org_study_id>Beijing302-005</org_study_id>
    <nct_id>NCT01662973</nct_id>
  </id_info>
  <brief_title>Umbilical Cord Mesenchymal Stem Cells for Patients With Primary Biliary Cirrhosis</brief_title>
  <official_title>Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Primary Biliary Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing 302 Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing 302 Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary biliary cirrhosis (PBC) is a slowly progressive disease that causes substantial loss&#xD;
      of intrahepatic bile ducts, ultimately resulting in cholestasis, advanced fibrosis,&#xD;
      cirrhosis, liver failure and even hepatocellular carcinoma. Histologically, the disease is&#xD;
      characterized by chronic portal inflammation with infiltration, destruction and loss of the&#xD;
      epithelial cells in the small-sized and medium-sized bile ducts. Currently, Ursodeoxycholic&#xD;
      acid (UDCA) in a dose of 13-15mg/kg/day is recommended as therapeutic drugs for PBC by AASLD&#xD;
      and is approved for this indication by the U.S. Food and Drug Administration (FDA). Treatment&#xD;
      with UDCA may delay disease progression and prolong survival free of liver transplantation.&#xD;
      However, one out of three patients does not adequately respond to UDCA therapy and many need&#xD;
      additional medical therapy or liver transplantation, or both. UC-MSC has been application for&#xD;
      the treatment of several severe autoimmune diseases, such as immune thrombocytopenia,&#xD;
      systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis. In this study, the&#xD;
      safety and efficacy of UC-MSC transplantation for PBC patients will be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic disease associated with&#xD;
      the development of cirrhosis and liver failure that may justify liver transplantation.&#xD;
      Ursodeoxycholic acid (UDCA) is currently the only drug approved specifically for the&#xD;
      treatment of PBC. However, one out of three patients does not adequately respond to UDCA&#xD;
      therapy and many need additional medical therapy or liver transplantation, or both.&#xD;
&#xD;
      The potential for stem cells to differentiate into biliary epithelial cells was recently&#xD;
      confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation&#xD;
      has been applicated in the clinic for treat several human disease such as GVHD, cardiac&#xD;
      injury and brain injury, and displayed good tolerance and efficiency. Recently, umbilical&#xD;
      cord-derived MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as&#xD;
      therapy-resistant rheumatoid arthritis and multiple sclerosis.&#xD;
&#xD;
      The purpose of this study is to learn whether and how UC-MSC can improve the disease&#xD;
      condition in patients with primary biliary cirrhosis. This study will also look at how well&#xD;
      UC-MSC is tolerated and its safety in PBC patients&#xD;
&#xD;
      Participants in the study will be randomly assigned to one of two treatment arms:&#xD;
&#xD;
      Arm A: Participants will receive 12 weeks of UC-MSC treatment plus UDCA. Arm B: Participants&#xD;
      will receive 12 weeks of placebo plus UDCA. UC-MSC will be prepared according to standard&#xD;
      procedures and is collected in plastic bags containing anticoagulant. UC-MSCs are given via&#xD;
      i.v. under sonography monitoring. After cell therapy, patients are followed up at week&#xD;
      4,8,12,24,36 and 48. The evaluation of some clinical parameters such as the level of serum&#xD;
      alkaline phosphatase (ALP), alanine aminotransferase(ALT) aspartate aminotransferase (AST)&#xD;
      and total bilirubin (TB), prothrombin time(PT), albumin(ALB), prealbumin(PA), are detected at&#xD;
      these time points. Mayo risk score, portal hypertension, Liver histology, MELD score and&#xD;
      clinical symptoms were also observed simultaneously.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2011</start_date>
  <completion_date type="Anticipated">October 2013</completion_date>
  <primary_completion_date type="Anticipated">October 2013</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>Serum alkaline phosphatase (ALP)</measure>
    <time_frame>0, 4, 8,12, 24, 36,48 weeks after treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Histological changes in liver biopsies</measure>
    <time_frame>baseline and 48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Bilirubin</measure>
    <time_frame>At base line and at week 4,8,12,24,36 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum AST</measure>
    <time_frame>At base line and at week 4,8,12,24,36 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mayo risk score</measure>
    <time_frame>At base line and at week 4,8,12,24,36 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Portal Hypertension after 12 weeks treatment</measure>
    <time_frame>At base line and at week 12,24,36 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MELD score</measure>
    <time_frame>At base line and at week 4,8,12,24,36 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with improvement of clinical symptoms</measure>
    <time_frame>At base line and at week 4,8,12,24,36 and 48</time_frame>
    <description>clinical symptoms including fatigue (Fatigue Impact Score, FIS) and pruritus ( Visual Analog Scale ,VAS)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Primary Biliary Cirrhosis</condition>
  <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 from day 0 through the week 12 study visit.&#xD;
Participants will then be followed until the week 48 study visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional plus placebo treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. 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 taken i.v., once per 4 week, at a dose of 1*10E6 UC-MSC/kg body weight for 12 weeks.</description>
    <arm_group_label>Conventional plus UC-MSC treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional plus placebo treatment</intervention_name>
    <description>Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks</description>
    <arm_group_label>Conventional plus placebo treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent&#xD;
&#xD;
          2. Primary Biliary Cirrhosis (according to the criteria defined by AASLD practice&#xD;
             guidelines , Hepatology, 2009;50:291-308 )&#xD;
&#xD;
          3. Negative pregnancy test (female patients in fertile age)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hepatocellular carcinoma or other Malignancies&#xD;
&#xD;
          2. Pregnant or lactating women&#xD;
&#xD;
          3. Viral Hepatitis ( HAB, HBV, HCV, et al )&#xD;
&#xD;
          4. Vital organs failure (Cardiac, Renal or Respiratory, et al)&#xD;
&#xD;
          5. Sepsis&#xD;
&#xD;
          6. Active thrombosis in the portal or hepatic veins&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fu-Sheng Wang, professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing 302 Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fu-Sheng Wang, professor</last_name>
    <phone>86-10-63879735</phone>
    <phone_ext>2015.12</phone_ext>
    <email>fswang302@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zheng Zhang, Doctor</last_name>
    <phone>86-10-63879735</phone>
    <phone_ext>2015.12</phone_ext>
    <email>Zhangzheng1975@yahoo.com.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Beijing 302 Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100039</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fu-Sheng Wang, professor</last_name>
      <phone>86-10-63879735</phone>
      <phone_ext>2015.12</phone_ext>
      <email>fswang302@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Lifeng Wang, Doctor</last_name>
      <phone>86-10-63879735</phone>
      <phone_ext>2015.12</phone_ext>
      <email>wanglf76@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Fu-Sheng Wang, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology. 1997 Sep;113(3):884-90. doi: 10.1016/s0016-5085(97)70183-5.</citation>
    <PMID>9287980</PMID>
  </reference>
  <reference>
    <citation>Kuiper EM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen TJ, Haagsma EB, Houben MH, Witteman BJ, van Erpecum KJ, van Buuren HR; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009 Apr;136(4):1281-7. doi: 10.1053/j.gastro.2009.01.003. Epub 2009 Jan 14.</citation>
    <PMID>19208346</PMID>
  </reference>
  <reference>
    <citation>Poupon R. Primary biliary cirrhosis: a 2010 update. J Hepatol. 2010 May;52(5):745-58. doi: 10.1016/j.jhep.2009.11.027. Epub 2010 Feb 18.</citation>
    <PMID>20347176</PMID>
  </reference>
  <reference>
    <citation>Silveira MG, Brunt EM, Heathcote J, Gores GJ, Lindor KD, Mayo MJ. American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. Hepatology. 2010 Jul;52(1):349-59. doi: 10.1002/hep.23637. No abstract available.</citation>
    <PMID>20578151</PMID>
  </reference>
  <verification_date>May 2013</verification_date>
  <study_first_submitted>August 5, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>May 30, 2013</last_update_submitted>
  <last_update_submitted_qc>May 30, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 31, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing 302 Hospital</investigator_affiliation>
    <investigator_full_name>Fu-Sheng Wang</investigator_full_name>
    <investigator_title>Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology</investigator_title>
  </responsible_party>
  <keyword>Primary Biliary Cirrhosis</keyword>
  <keyword>Mesenchymal Stem Cells</keyword>
  <keyword>Serum alkaline phosphatase</keyword>
  <keyword>Serum Bilirubin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Liver Cirrhosis, Biliary</mesh_term>
    <mesh_term>Fibrosis</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/NCT01662973
org study id: Beijing302-005
nct id: NCT01662973
lead sponsor: 
has dmc: Yes
Primary biliary cirrhosis (PBC) is a slowly progressive disease that causes substantial loss
      of intrahepatic bile ducts, ultimately resulting in cholestasis, advanced fibrosis,
      cirrhosis, liver failure and even hepatocellular carcinoma. Histologically, the disease is
      characterized by chronic portal inflammation with infiltration, destruction and loss of the
      epithelial cells in the small-sized and medium-sized bile ducts. Currently, Ursodeoxycholic
      acid (UDCA) in a dose of 13-15mg/kg/day is recommended as therapeutic drugs for PBC by AASLD
      and is approved for this indication by the U.S. Food and Drug Administration (FDA). Treatment
      with UDCA may delay disease progression and prolong survival free of liver transplantation.
      However, one out of three patients does not adequately respond to UDCA therapy and many need
      additional medical therapy or liver transplantation, or both. UC-MSC has been application for
      the treatment of several severe autoimmune diseases, such as immune thrombocytopenia,
      systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis. In this study, the
      safety and efficacy of UC-MSC transplantation for PBC patients will be evaluated.
Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic disease associated with
      the development of cirrhosis and liver failure that may justify liver transplantation.
      Ursodeoxycholic acid (UDCA) is currently the only drug approved specifically for the
      treatment of PBC. However, one out of three patients does not adequately respond to UDCA
      therapy and many need additional medical therapy or liver transplantation, or both.

      The potential for stem cells to differentiate into biliary epithelial cells was recently
      confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation
      has been applicated in the clinic for treat several human disease such as GVHD, cardiac
      injury and brain injury, and displayed good tolerance and efficiency. Recently, umbilical
      cord-derived MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as
      therapy-resistant rheumatoid arthritis and multiple sclerosis.

      The purpose of this study is to learn whether and how UC-MSC can improve the disease
      condition in patients with primary biliary cirrhosis. This study will also look at how well
      UC-MSC is tolerated and its safety in PBC patients

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

      Arm A: Participants will receive 12 weeks of UC-MSC treatment plus UDCA. Arm B: Participants
      will receive 12 weeks of placebo plus UDCA. UC-MSC will be prepared according to standard
      procedures and is collected in plastic bags containing anticoagulant. UC-MSCs are given via
      i.v. under sonography monitoring. After cell therapy, patients are followed up at week
      4,8,12,24,36 and 48. The evaluation of some clinical parameters such as the level of serum
      alkaline phosphatase (ALP), alanine aminotransferase(ALT) aspartate aminotransferase (AST)
      and total bilirubin (TB), prothrombin time(PT), albumin(ALB), prealbumin(PA), are detected at
      these time points. Mayo risk score, portal hypertension, Liver histology, MELD score and
      clinical symptoms were also observed simultaneously.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serum alkaline phosphatase (ALP)
time frame: 0, 4, 8,12, 24, 36,48 weeks after treatment
measure: Histological changes in liver biopsies
time frame: baseline and 48 weeks
measure: Serum Bilirubin
time frame: At base line and at week 4,8,12,24,36 and 48
measure: Serum AST
time frame: At base line and at week 4,8,12,24,36 and 48
measure: Mayo risk score
time frame: At base line and at week 4,8,12,24,36 and 48
measure: Number of patients with Portal Hypertension after 12 weeks treatment
time frame: At base line and at week 12,24,36 and 48
measure: MELD score
time frame: At base line and at week 4,8,12,24,36 and 48
measure: Number of participants with improvement of clinical symptoms
time frame: At base line and at week 4,8,12,24,36 and 48
description: clinical symptoms including fatigue (Fatigue Impact Score, FIS) and pruritus ( Visual Analog Scale ,VAS)
arm group label: Conventional plus UC-MSC treatment
arm group type: Experimental
description: Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit.
Participants will then be followed until the week 48 study visit.
arm group label: Conventional plus placebo treatment
arm group type: Placebo Comparator
description: Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. 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 taken i.v., once per 4 week, at a dose of 1*10E6 UC-MSC/kg body weight for 12 weeks.
arm group label: Conventional plus UC-MSC treatment
intervention type: Other
intervention name: Conventional plus placebo treatment
description: Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks
arm group label: Conventional plus placebo treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Fu-Sheng Wang, professor
role: Principal Investigator
affiliation: Beijing 302 Hospital
last name: Fu-Sheng Wang, professor
phone: 86-10-63879735
phone ext: 2015.12
email: fswang302@163.com
last name: Zheng Zhang, Doctor
phone: 86-10-63879735
phone ext: 2015.12
email: Zhangzheng1975@yahoo.com.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
citation: Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology. 1997 Sep;113(3):884-90. doi: 10.1016/s0016-5085(97)70183-5.
PMID: 9287980
citation: Kuiper EM, Hansen BE, de Vries RA, den Ouden-Muller JW, van Ditzhuijsen TJ, Haagsma EB, Houben MH, Witteman BJ, van Erpecum KJ, van Buuren HR; Dutch PBC Study Group. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid. Gastroenterology. 2009 Apr;136(4):1281-7. doi: 10.1053/j.gastro.2009.01.003. Epub 2009 Jan 14.
PMID: 19208346
citation: Poupon R. Primary biliary cirrhosis: a 2010 update. J Hepatol. 2010 May;52(5):745-58. doi: 10.1016/j.jhep.2009.11.027. Epub 2010 Feb 18.
PMID: 20347176
citation: Silveira MG, Brunt EM, Heathcote J, Gores GJ, Lindor KD, Mayo MJ. American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. Hepatology. 2010 Jul;52(1):349-59. doi: 10.1002/hep.23637. No abstract available.
PMID: 20578151
responsible party type: Principal Investigator
investigator affiliation: Beijing 302 Hospital
investigator full name: Fu-Sheng Wang
investigator title: Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology
mesh term: Liver Cirrhosis
mesh term: Liver Cirrhosis, Biliary
mesh term: Fibrosis