UC-MSC Infusion for HBV-Related Acute-on-Chronic Liver Failure

Umbilical Cord Blood Derived Mesenchymal Stem Cells Infusion for HBV-Related Acute-on-Chronic Liver Failure: A Randomized Controlled Trial

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.

Study Overview

• Status: Unknown
• Conditions: Liver Failure
• Intervention / Treatment: Drug: umbilical cord blood mesenchymal stem cells

• Study Type: Interventional
• Enrollment (Anticipated): 261
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group MSC-1; Patients in Group MSC-1 received standard medical treatment and infusions of umbilical cord blood mesenchymal stem cells via peripheral veins once a week for 8 weeks.	Drug: umbilical cord blood mesenchymal stem cells
Experimental: Group MSC-2; Patients in Group MSC-1 received standard medical treatment and infusions of umbilical cord blood mesenchymal stem cells via peripheral veins once a week for 4 weeks.	Drug: umbilical cord blood mesenchymal stem cells
No Intervention: Group Control; Patients in Group Control received standard medical treatment, including bed rest, nutritional supplementation, administration of human serum albumin (10g per day until serum albumin was 35g/L) and plasma (200 ml to 400 ml per day until the international normalized ratio was less than 1.5), anti-viral therapy, glycyrrhizin,S-adenosylmethionine and appropriate treatment for complications (such as infection, encephalopathy, hepatorenal syndrome and intestinal paralysis).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of adverse reactions after umbilical cord blood derived mesenchymal stem cells (UC-MSC) infusions.	52 weeks
The survival time of patients after UC-MSC infusions.	52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The influence on levels of ALT (U/L) and AST (U/L) after UC-MSC infusions	1,2,3,4,8,12,24,36,52weeks
The influence on levels of ALB(g/L) after UC-MSC infusions	1,2,3,4,8,12,24,36,52weeks
The influence on levels of TBil (umol/L) after UC-MSC infusions	1,2,3,4,8,12,24,36,52weeks
The influence on levels of INR after UC-MSC infusions	1,2,3,4,8,12,24,36,52weeks
The influence on levels of MELD score, SOFA score and CTP score after UC-MSC infusions	1,2,3,4,8,12,24,36,52weeks
The incidence of fatal complications after UC-MSC infusions.	52 weeks
Comparison of levels of NKG2A among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of NKG2D among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of NKP46 among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of KIR2DL1 among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of KIR2DL3 among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of KIR3DL1 among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of perforin among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of FasL among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks
Comparison of levels of gramzymeB among the groups after UC-MSC infusions	2,4,8,12,24,36,52 weeks

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: June 21, 2016
• First Posted (Estimate): June 24, 2016

Study Record Updates

• Last Update Posted (Estimate): June 24, 2016
• Last Update Submitted That Met QC Criteria: June 21, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: UCBMSC; LBingliang (Registry Identifier: Bing-liang Lin)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED