Umbilical Cord Mesenchymal Stem Cells for Patients With Primary Biliary Cirrhosis

Phase 1

• Conditions: Primary Biliary Cirrhosis
• Interventions: Other: conventional plus UC-MSC treatment; Other: Conventional plus placebo treatment

• Registration Number: NCT01662973
• Lead Sponsor: Beijing 302 Hospital

Brief Summary

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.

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.

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2012-08-05
• Study First Submitted QC: 2012-08-09
• Study First Posted: 2012-08-13
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-30
• Last Update Posted: 2013-05-31
• Primary Completion: 2013-10
• Study Completion: 2013-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional plus UC-MSC treatment	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.
Conventional plus placebo treatment	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.

Primary Outcome Measures

Name	Time	Method
Serum alkaline phosphatase (ALP)	0, 4, 8,12, 24, 36,48 weeks after treatment

Secondary Outcome Measures

Name	Time	Method
Number of patients with Portal Hypertension after 12 weeks treatment	At base line and at week 12,24,36 and 48
Histological changes in liver biopsies	baseline and 48 weeks
Serum Bilirubin	At base line and at week 4,8,12,24,36 and 48
Serum AST	At base line and at week 4,8,12,24,36 and 48
Mayo risk score	At base line and at week 4,8,12,24,36 and 48
MELD score	At base line and at week 4,8,12,24,36 and 48
Number of participants with improvement of clinical symptoms	At base line and at week 4,8,12,24,36 and 48	clinical symptoms including fatigue (Fatigue Impact Score, FIS) and pruritus ( Visual Analog Scale ,VAS)

Trial Locations

Locations (1)

Beijing 302 Hospital; 🇨🇳 Beijing, Beijing, China