Umbilical Cord Mesenchymal Stem Cells for Patients With Primary Biliary Cirrhosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Beijing 302 Hospital
Sponsor:
Information provided by (Responsible Party):
Fu-Sheng Wang, Beijing 302 Hospital
ClinicalTrials.gov Identifier:
NCT01662973
First received: August 5, 2012
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Primary Biliary Cirrhosis
Other: conventional plus UC-MSC treatment
Other: Conventional plus placebo treatment
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by Beijing 302 Hospital:

Primary Outcome Measures:
  • Serum alkaline phosphatase (ALP) [ Time Frame: 0, 4, 8,12, 24, 36,48 weeks after treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Histological changes in liver biopsies [ Time Frame: baseline and 48 weeks ] [ Designated as safety issue: No ]
  • Serum Bilirubin [ Time Frame: At base line and at week 4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
  • Serum AST [ Time Frame: At base line and at week 4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
  • Mayo risk score [ Time Frame: At base line and at week 4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
  • Number of patients with Portal Hypertension after 12 weeks treatment [ Time Frame: At base line and at week 12,24,36 and 48 ] [ Designated as safety issue: No ]
  • MELD score [ Time Frame: At base line and at week 4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
  • Number of participants with improvement of clinical symptoms [ Time Frame: At base line and at week 4,8,12,24,36 and 48 ] [ Designated as safety issue: No ]
    clinical symptoms including fatigue (Fatigue Impact Score, FIS) and pruritus ( Visual Analog Scale ,VAS)


Estimated Enrollment: 100
Study Start Date: October 2011
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Conventional plus UC-MSC treatment

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.

Other: conventional plus UC-MSC treatment
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.
Placebo Comparator: Conventional plus placebo treatment
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.
Other: Conventional plus placebo treatment
Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent
  2. Primary Biliary Cirrhosis (according to the criteria defined by AASLD practice guidelines , Hepatology, 2009;50:291-308 )
  3. Negative pregnancy test (female patients in fertile age)

Exclusion Criteria:

  1. Hepatocellular carcinoma or other Malignancies
  2. Pregnant or lactating women
  3. Viral Hepatitis ( HAB, HBV, HCV, et al )
  4. Vital organs failure (Cardiac, Renal or Respiratory, et al)
  5. Sepsis
  6. Active thrombosis in the portal or hepatic veins
  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: NCT01662973

Contacts
Contact: Fu-Sheng Wang, professor 86-10-63879735 ext 2015.12 fswang302@163.com
Contact: Zheng Zhang, Doctor 86-10-63879735 ext 2015.12 Zhangzheng1975@yahoo.com.cn

Locations
China, Beijing
Beijing 302 Hospital Recruiting
Beijing, Beijing, China, 100039
Contact: Fu-Sheng Wang, professor    86-10-63879735 ext 2015.12    fswang302@163.com   
Contact: Lifeng Wang, Doctor    86-10-63879735 ext 2015.12    wanglf76@gmail.com   
Principal Investigator: Fu-Sheng Wang, Professor         
Sponsors and Collaborators
Beijing 302 Hospital
Investigators
Principal Investigator: Fu-Sheng Wang, professor Beijing 302 Hospital
  More Information

Publications:
Responsible Party: Fu-Sheng Wang, Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology, Beijing 302 Hospital
ClinicalTrials.gov Identifier: NCT01662973     History of Changes
Other Study ID Numbers: Beijing302-005
Study First Received: August 5, 2012
Last Updated: May 30, 2013
Health Authority: China: Ministry of Health

Keywords provided by Beijing 302 Hospital:
Primary Biliary Cirrhosis
Mesenchymal Stem Cells
Serum alkaline phosphatase
Serum Bilirubin

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Cirrhosis, Biliary
Bile Duct Diseases
Biliary Tract Diseases
Cholestasis
Cholestasis, Intrahepatic
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on October 23, 2014