Mesenchymal Stem Cell Transplantation for Refractory Primary Biliary Cholangitis

Study Overview
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Brief Summary
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Ursodeoxycholic acid is the mainstay treatment medicine for primary biliary cholangitis(PBC). About 1/3 of the patients do not respond to UDCA, which is defined as refractory PBC. Mesenchymal stem cells (MSC) has been reported to improve the outcomes of PBC patients. Randomization controlled studies are needed to confirm the long term effect of MSC treatment for refractory PBC. This study aimed to investigate the safety and efficacy of mesenchymal stem cells in PBC patients that do not respond to UDCA treatment. This study is an double-blind multicenter randomized and placebo-controlled study. Patients with with refractory PBC will be randomly assigned to receive MSC treatment plus UDCA or UDCA alone (control). Three times of MSC infusion (0.1-1x10E6 cells/kg body weight) via peripheral vein will be given to the experimental group (once in 4 weeks). The primary outcome is absolute change in alkaline phosphatase. Secondary outcomes are changes of other liver function indices such as ALT TBIL AST GGT, improve of symptoms and liver histology.

Official Title
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Mesenchymal Stem Cell Transplantation for Refractory Primary Biliary Cholangitis, a Randomized Double-blind Placebo Controlled Trial

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent Age between 18-70 years old BMI between 17-28 Meeting at least 2 of the 3 criteria: (1) positive for anti-mitochondial antibody (AMA)；(2) Elevated ALP or GGT；(3) PBC diagnosis confirmed by liver biopsy Serum ALP >/=1.67 ULN after at leat 6 months treatment with UDCA 1(3-17mg/kg/day) - Exclusion Criteria: Pregnancy, breast-feeding females Use of liver-toxic drugs over 2 week within 6 months prior to recruitment； refractory variceal bleeding, uncontrolled hepatoencephalopathy or uncontrolled ascites. Acute of chronic kidney failure. Commodities with other liver diseases such as viral hepatitis, alcoholic liver disease, auto-immune hepatitis or liver cancer Severe cardiovascular disease； liver transplantation listed patients； ALT/AST over 5xULN，or total bilirubin >85umol/l anticipated need for liver transplantation within 1 year according to mayo risk score Other candidates who are judged to be not applicable to this study by doctors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC group<br>mesenchymal stem cell transplantation via peripheral vein: 0.1-1x10E6 MSCs/kg body weight administered via peripheral vein at week 0, 4, 8 plus UDCA. | Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein<br>* 0.1-1x10E6 MSCs/kg body weight will be administered via peripheral vein for 3 times at week 0, 4 and 8 mesenchymal stem cell mesenchymal stem cell infusion produced by Cell products of National Engineering Research Center(short for CPNERC), Tianjin, China For control group, placebo infusions will be given to the participants at the same time points<br>|
| Placebo Comparator: control<br>placebo infusions (placebo infusion differs from the experimental infusion in only that placebo has no mesenchymal stem cells) will be administered via peripheral vein at week 0, 4, 8 plus UDCA. | Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein<br>* 0.1-1x10E6 MSCs/kg body weight will be administered via peripheral vein for 3 times at week 0, 4 and 8 mesenchymal stem cell mesenchymal stem cell infusion produced by Cell products of National Engineering Research Center(short for CPNERC), Tianjin, China For control group, placebo infusions will be given to the participants at the same time points<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of alkaline phosphatase (ALP) | The absolute value change of ALP after 1 year of the initial stem cell treatment | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of other liver function indices | The absolute value change of total bilirubin, ALT, AST, GGT after initial stem cell treatment | 1 year | 
| Change of liver histology | histological scores assessed by liver biopsy at baseline and after treatment | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Biliary Cirrhosis (now termed as primary biliary cholangitis), mesenchymal stem cell,