Clinical trial NCT02812121: UC-MSC Infusion for HBV-Related Acute-on-Chronic Liver Failure
Official title: Umbilical Cord Blood Derived Mesenchymal Stem Cells Infusion for HBV-Related Acute-on-Chronic Liver Failure: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Failure
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-06-24
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is a severe disease with high mortality. Our previous study have demonstrated that peripheral infusion of bone marrow-derived mesenchymal stromal cells (MSCs) weekly for 4 times is safe and improves 24 weeks survival rate of ACLF patients. In this study, we intend to assess the safety and efficacy of umbilical cord blood derived MSCs for HBV-related ACLF patients.


Eligibility criteria: Inclusion Criteria:

1. Patients with ACLF-which is characterized by acute hepatic insult manifesting as jaundice (serum total bilirubin ≥ 10×ULN umol/L) and coagulopathy (international normalized ratio≥ 1.5 or prothrombin activity \< 40%), complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination, in patients with previously diagnosed or undiagnosed chronic liver disease;
2. Positive serum hepatitis B surface antigen (HBsAg) for more than 6 months;
3. End-stage liver disease scores ranging from 17-30,; 4.18-65 years of age.

Exclusion Criteria:

1. Serious complications within the previous 2 months (e.g. gastrointestinal bleeding, serious infection );
2. Concomitant autoimmune disease;
3. Superinfection with other hepatitis viruses;
4. Important organ dysfunctions not due to liver disease or malignancies;
5. Pregnancy and lactation;
6. Liver tumor or nodules secondary to cirrhosis proven by ultrasound, computerized tomography (CT), or magnetic resonance (MR) imaging;
7. Bioartificial liver support therapy;
8. Previous liver transplantation.

Primary outcomes:
measure: The incidence of adverse reactions after umbilical cord blood derived mesenchymal stem cells (UC-MSC) infusions.
timeFrame: 52 weeks
measure: The survival time of patients after UC-MSC infusions.
timeFrame: 52 weeks
Secondary outcomes:
measure: The influence on levels of ALT (U/L) and AST (U/L) after UC-MSC infusions
timeFrame: 1,2,3,4,8,12,24,36,52weeks
measure: The influence on levels of ALB(g/L) after UC-MSC infusions
timeFrame: 1,2,3,4,8,12,24,36,52weeks
measure: The influence on levels of TBil (umol/L) after UC-MSC infusions
timeFrame: 1,2,3,4,8,12,24,36,52weeks
measure: The influence on levels of INR after UC-MSC infusions
timeFrame: 1,2,3,4,8,12,24,36,52weeks
measure: The influence on levels of MELD score, SOFA score and CTP score after UC-MSC infusions
timeFrame: 1,2,3,4,8,12,24,36,52weeks
measure: The incidence of fatal complications after UC-MSC infusions.
timeFrame: 52 weeks
measure: Comparison of levels of NKG2A among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of NKG2D among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of NKP46 among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of KIR2DL1 among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of KIR2DL3 among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of KIR3DL1 among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of perforin among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of FasL among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
measure: Comparison of levels of gramzymeB among the groups after UC-MSC infusions
timeFrame: 2,4,8,12,24,36,52 weeks
Other outcomes:
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