MSC-EV in Acute-on-Chronic Liver Failure After Liver Transplantation

October 10, 2023 updated by: Yang Yang, Third Affiliated Hospital, Sun Yat-Sen University

Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute-on-Chronic Liver Failure After Liver Transplantationa：a Prospective, Randomized, Controlled Clinical Study

Acute-on-chronic liver failure refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors. Liver transplantation is the only curative treatment for this type of end-stage liver disease. The potential of MSCs to repair or regenerate damaged tissue and suppress immune responses makes them promising in the treatment of liver diseases, especially in the field of liver transplantation. Many studies have shown that MSC-based therapies can reduce the symptoms of liver disease due to their paracrine effects. Therefore, compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EV) are gradually gaining attention for their enhanced safety, as they do not replicate or cause microvascular embolism, and can be easily stored without losing their properties. It represents a novel and effective cell-free therapeutic agent as alternative to cell-based therapies for liver diseases, and liver failure was also concerned. This study was designed to evaluate the safety and tolerability of MSC-EV in acute-on-chronic liver failure after liver transplantation.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

In the MSC-EV group (experimental group), 15 patients will receive a single injection of MSC-EV after their first liver transplantation. In the non-MSC-EV group (control group), 15 patients will not receive MSC-EV therapy after their first liver transplantation.

The outcome of the experimental group will be compared with that of similar control patients undergoing liver transplantation but who will not receive MSC-EV. Both of the two groups will receive standard immunosuppressive therapy( a regimen based on tacrolimus (TAC), mycophenolate mofetyl (MMF) and steroids). Patients participated in the experimental cohort will be infused with a single dose of 10 E10 MSC-EV particles per 100ml, at an appropriate time during the first 1-5 days after transplantation.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Yang Yang, PHD, MD
  • Phone Number: 020-85252113
  • Email: yysysu@163.com

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510630
        • Third Affiliated Hospital, Sun Yat-Sen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • aged 18-60 years;
  • Acute on chronic liver failure-which is characterized by acute hepatic insult manifesting as jaundice (serum total bilirubin [TBil] ≥ 10×ULN umol/L) and coagulopathy (international normalized ratio [INR] ≥ 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; Requiring liver transplantation due to acute on chronic liver failure;
  • Obtain the patients' consent after informing patients of the purpose and method of the clinical trial;

Exclusion Criteria:

  • Past history of malignant disease
  • Active uncontrolled infection;
  • Combined transplantation
  • EBV-negative;
  • HIV or HCV positive;
  • Retransplantation;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MSC-EV group
After liver transplantation, on the basis of postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.), an additional injection of MSC-EV will be received between the 1st and 5th days after transplantation
Biological: MSC-EV
10 E10 MSC-EV particles per 100ml for a single dose. No prior HLA matching between MSC donors and recipients or liver donors
No Intervention: Non-MSC-EV group
After liver transplantation, patients will receive postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.
Time Frame: 24 hours after injection
Incidence, timing and severity of any clinical complication related to MSC-EV infusion, such as tympanic body temperature, heart rate, mean arterial blood pressure and allergy, as assessed by CTCAE v4.0 .
24 hours after injection
Aspartate aminotransferase (AST)
Time Frame: 6 months after transplantation
Collect clinical results reflecting liver function
6 months after transplantation
Alanine aminotransferase (ALT)
Time Frame: 6 months after transplantation
Collect clinical results reflecting liver function
6 months after transplantation
Bilirubin level
Time Frame: 6 months after transplantation
Collect clinical results reflecting liver function
6 months after transplantation
International normalized ratio (INR)
Time Frame: 6 months after transplantation
Collect clinical results reflecting liver function
6 months after transplantation
carbohydrate Compound antigen (GGT) level
Time Frame: 6 months after transplantation
Collect clinical results reflecting liver function
6 months after transplantation
Adverse events
Time Frame: 6 months
Any adverse events which may related to MSC-EV infusion
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of survived patients at 1 year after liver transplantation, according to the follow-up results.
Time Frame: 12 months
Patients who are surviving, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation
12 months
Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.
Time Frame: 12 months
Surviving patients with primary and functional grafts, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation.
12 months
Recipient's immune function, as assessed by analysis of immune cell subsets from biopsy or blood samples ,at months 1-6 after liver transplantation.
Time Frame: 6 months
A series of immune cell subsets will be analyzed, including T cells (CD3+), CD4+ T cells (CD3+ CD4+ lymphocytes), CD8+ T cells (CD3+ CD8+ lymphocytes), naïve CD4+ T cells (CD4+ CD45RAhigh lymphocytes), memory CD4+ T cells (CD4+ CD45RO+ lymphocytes), natural killer (NK) cells (CD3- CD56+ lymphocytes), as well as B cells (CD19+ lymphocytes)
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University

Investigators

  • Principal Investigator: Yang Yang, PHD, MD, Third Affiliated Hospital, Sun Yat-Sen University, guangzhou, Guangdong, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 30, 2023

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

May 8, 2023

First Submitted That Met QC Criteria

May 30, 2023

First Posted (Actual)

May 31, 2023

Study Record Updates

Last Update Posted (Actual)

October 12, 2023

Last Update Submitted That Met QC Criteria

October 10, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MSC-EV of ThirdSunYatSen

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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