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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Procedure: mesenchymal stem cell transplantation or placebo infusion via peripheral vein

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Changcun Guo
      • Contact: Changcun Guo; Phone Number: 13991900180; Email: guochc@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC group; 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; 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
Placebo Comparator: control; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Acute-On-Chronic Liver Failure, mesenchymal stem cell,
• 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: KY20172049-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study protocol, statistical analysis processes and clinical data of individual participants will be shared.
• IPD Sharing Time Frame: within 12 months after the study completion and before publications of the findings.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No