Mesenchymal Stem Cell Transplantation for Acute-on-chronic Liver Failure

Study Overview
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Brief Summary
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Mesenchymal stem cells (MSC) has been reported to improved outcomes of acute-on-chronic liver failure(ACLF). More randomization controlled studies are needed to confirm the effect of MSC treatment for ACLF. This study aimed to investigate the efficacy of mesenchymal stem cells in ACLF patients. This study is an double-blind multicenter randomized and placebo-controlled study. Patients with with ACLF will be randomly assigned to receive MSC treatment (experimental) or standard medical treatment (control). Three times of MSC infusion (0.1-1x10E6cells/kg body weight) via peripheral vein will be given to the experimental group (once per week). The primary outcome is 12 week mortality. Secondary outcomes are clinical remission rate and changes of liver function indices and liver function scores.

Official Title
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Mesenchymal Stem Cell Transplantation for Acute-on-chronic Liver Failure, a Randomized, Double Blind, Placebo Controlled Trial

Conditions
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Acute-On-Chronic Liver Failure

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: Age between 18-70 years old Meeting the criteria of ACLF defined as: 1. definitive chronic liver diseases, acute decompensation within 4 weeks; 2. Significant GI symptom as such fatigue, jaundice,; 3. total bilirubin (TBIL) ≥170 µmo1/L or daily increase of TBIL ≥17.1 µmo1/L; 4. PTA≤40% or INR≥ 1.5; 5. Decompensation of liver functions such as ascites or hepatoencephalopathy; MELD score between 17-30. (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643) Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases Informed consent Exclusion Criteria: Sever complications with 30 days ( GI bleeding, severe infection)； --liver cancer or other malignancies patients on liver transplantation list patients with uncontrolled infections severe renal failure Severe chronic obstructive pulmonary disease COPD (GOLD III-IV) Extrahepatic cholanstasis patients due to biliary obstruction. HIV infection Pregnant or breast-feeding females. Enrolled in other clinical trials with 3 months other conditions considered inappropriate for the study

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, 1, 2 weeks | 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, 1, 2 | 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 |
| --- | --- | --- |
| Efficacy: 12 week mortality rate | mortality rate assessed at week 12 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission rate at week 12 | Clinical remission define as: significant improvement of symptoms and resolution of hepatoencephalopathy; TBIL decrease to below 5 times of ULN，PTA>40% or INR<1.6 | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute-On-Chronic Liver Failure, mesenchymal stem cell,