Umbilical Cord Mesenchymal Stem Cells for Patients With Primary Biliary Cirrhosis
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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 |
- Serum alkaline phosphatase (ALP) [ Time Frame: 0, 4, 8,12, 24, 36,48 weeks after treatment ] [ Designated as safety issue: No ]
- 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 |
Inclusion Criteria:
- Written informed consent
- Primary Biliary Cirrhosis (according to the criteria defined by AASLD practice guidelines , Hepatology, 2009;50:291-308 )
- Negative pregnancy test (female patients in fertile age)
Exclusion Criteria:
- Hepatocellular carcinoma or other Malignancies
- Pregnant or lactating women
- Viral Hepatitis ( HAB, HBV, HCV, et al )
- Vital organs failure (Cardiac, Renal or Respiratory, et al)
- Sepsis
- Active thrombosis in the portal or hepatic veins
Contacts and Locations| 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 |
| 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 | |
| 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: | August 9, 2012 |
| 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, Biliary Liver Cirrhosis Fibrosis Cholestasis, Intrahepatic Cholestasis |
Bile Duct Diseases Biliary Tract Diseases Digestive System Diseases Liver Diseases Pathologic Processes |
ClinicalTrials.gov processed this record on May 16, 2013