Mesenchymal Stem Cell Transplantation for Refractory Primary Biliary Cholangitis

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

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.

Study Overview

• Status: Unknown
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ying Han, MD; Phone Number: 862984771539; Email: guochc@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Changcun Guo
      • Contact: Changcun Guo; Phone Number: 13991900180; Email: guochc@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. informed consent
2. Age between 18-70 years old
3. BMI between 17-28
4. 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
5. Serum ALP >/=1.67 ULN after at leat 6 months treatment with UDCA 1(3-17mg/kg/day) -

Exclusion Criteria:

1. Pregnancy, breast-feeding females
2. Use of liver-toxic drugs over 2 week within 6 months prior to recruitment；
3. refractory variceal bleeding, uncontrolled hepatoencephalopathy or uncontrolled ascites.
4. Acute of chronic kidney failure.
5. Commodities with other liver diseases such as viral hepatitis, alcoholic liver disease, auto-immune hepatitis or liver cancer
6. Severe cardiovascular disease；
7. liver transplantation listed patients；
8. ALT/AST over 5xULN，or total bilirubin >85umol/l
9. anticipated need for liver transplantation within 1 year according to mayo risk score
10. Other candidates who are judged to be not applicable to this study by doctors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC group; 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; 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
Placebo Comparator: control; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Primary Biliary Cirrhosis (now termed as primary biliary cholangitis), mesenchymal stem cell,
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Fibrosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: KY20172050-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: The data will be available after the completion of the study and before publications for 1 year
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No