Clinical trial NCT03668145: Mesenchymal Stem Cell Transplantation for Refractory Primary Biliary Cholangitis
Official title: Mesenchymal Stem Cell Transplantation for Refractory Primary Biliary Cholangitis, a Randomized Double-blind Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Primary Biliary Cirrhosis
Keywords: Primary Biliary Cirrhosis (now termed as primary biliary cholangitis), mesenchymal stem cell,
Lead sponsor: Xijing Hospital of Digestive Diseases
Sponsor class: OTHER
First posted: 2018-09-12
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change of alkaline phosphatase (ALP)
timeFrame: 1 year
Secondary outcomes:
measure: Change of other liver function indices
timeFrame: 1 year
measure: Change of liver histology
timeFrame: 1 year
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Changcun Guo
state: Shaanxi
Study officials:
References: