Efficacy and Safety Study of Allogenic Mesenchymal Stem Cells for Patients With Refractory Primary Biliary Cirrhosis

Phase 1

• Conditions: Primary Biliary Cirrhosis
• Interventions: Drug: ursodeoxycholic acid

• Registration Number: NCT01440309
• Lead Sponsor: Robert Chunhua Zhao, MD, PhD

Brief Summary

The study is designed to evaluate the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells for patients with refractory primary biliary cirrhosis (PBC).

Detailed Description

Primary biliary cirrhosis (PBC) is an organ-specific inflammatory disease and characterized by immune mediated destruction of intrahepatic bile ducts, then lead to liver cirrhosis and eventually failure.Currently, ursodeoxycholic acid (UDCA) is the only drug approved by the Food and Drug Administration (FDA). Novel treatment is urgently needed for patients who have an incomplete response to UDCA. Mesenchymal stem cells (MSC) represent a promising tool for cell-based therapies of autoimmune diseases. To explore the therapeutic effect of MSCs for PBC, the investigators plan to conduct an open-label, randomized clinical trial. Patients with PBC will be enrolled and randomly divided into two groups which will receive MSCs and UDCA respectively. The investigators will evaluate the efficacy and safety of MSCs for PBC by comparison of symptom improvement, survival rate and side effects in the two groups.

Study Timeline

• Status Verified: 2011-09
• Study First Submitted: 2011-09-20
• Study First Submitted QC: 2011-09-23
• Study First Posted: 2011-09-26
• Study Start: 2011-11
• Last Update Submitted: 2012-08-01
• Last Update Posted: 2012-08-03
• Primary Completion: 2013-11
• Study Completion: 2013-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• There must be at least two of the following: a concentration in serum of AMAs at titres of 1:40 or higher; an unexplained rise in the amount of alkaline phosphatase of at least 1•5 times the upper limit of normal for more than 24 weeks; and compatible liver histological findings, specifically non-suppurative cholangitis and interlobular bile duct injury.
• Incomplete response to UDCA at 13-15 mg/kg/day, Criteria for the group of complete responders is including: concentrations of alkaline phosphatase less than three times the upper limit of normal, aspartate aminotransferase less than twice the upper limit of normal, and bilirubin less than 17 μmol/L;and normalisation of abnormal concentrations of bilirubin, albumin, or both.
• Liver pathological staging in 2 or3, Histological staging is based on Ludwig's and Scheuer's classifications

Exclusion Criteria

• Patients are receiving any other investigational agents within 4 weeks of study entry
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia
• In pregnancy or lactation
• Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
• HCVpositive ，HBSAg positive or with other liver diseases
• Combined with other autoimmune disease
• Expected survival time is less than one year
• Decompensation of liver function（Child B or C）
• Have a history of allergy or Allergic constitution

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ursodeoxycholic acid (UDCA)	ursodeoxycholic acid	Patients who have primary biliary cirrhosis.

Primary Outcome Measures

Name	Time	Method
serum level of alkaline phosphatase	24 months after MSCs administration	Serum level of alkaline phosphatase will be measured at entry, 1 months，3 months, 6 months and 24 months after therapy

Secondary Outcome Measures

Name	Time	Method
histological changes in liver biopsies	6 months after therapy	Liver biopsy of each patient will be taken before entry into therapeutic trials and at 6 months after therapy.
Serum levels of TNF-alpha	6 months after therapy	serum levels of TNF-alpha will be assessed before entry into therapeutic trials and at 6 months after therapy
changes in fatigue	6 months after theraphy	changes in fatigue will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by PBC-40 score.
The occurrence of cirrhosis and its complications	24 months after therapy
Serum levels of Interleukin	6 months after therapy	serum levels of Interleukin will be assessed before entry into therapeutic trials and at 6 months after therapy
changes in pruritus severity	6 months after therapy	changes in pruritus severity will be evaluated before test (baseline), 1 month,3 months and 6 months after theraphy by VAS score.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China