Mesenchymal Stem Cell Transplantation for Refractory Primary Biliary Cholangitis

Xijing Hospital of Digestive Diseases

Status: Unknown

Conditions: Primary Biliary Cirrhosis

Treatments: Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein

Study type: Interventional

Funder types: Other

Identifiers

NCT03668145

KY20172050-1

Details and patient eligibility

About

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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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140 participants in 2 patient groups, including a placebo group

MSC group

Experimental group

Description:

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.

Treatment:

Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein

control

Placebo Comparator group

Description:

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.

Treatment:

Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein