MSC-EVs in Acute/ Acute-on-Chronic Liver Failure After Liver Transplantation

NCT06825572 | Not Yet Recruiting Phase 1

• 1 other identifier: MSC-EVs of ThirdSunYatSen
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Acute liver failure (ALF) refers to a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. 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.

Conditions

Liver Failure; Mesenchymal Stem Cell; Extracellular Vesicles

Keywords

MSC-EV; Liver transplantation; Liver failure

Outcome Measures

Primary Outcomes (7)

• Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.

  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)

  Collect clinical results reflecting liver function

  6 months after transplantation

• Alanine aminotransferase (ALT)

  Collect clinical results reflecting liver function

  6 months after transplantation

• Bilirubin level

  Collect clinical results reflecting liver function

  6 months after transplantation

• International normalized ratio (INR)

  Collect clinical results reflecting liver function

  6 months after transplantation

• carbohydrate Compound antigen (GGT) level

  Collect clinical results reflecting liver function

  6 months after transplantation

• Adverse events

  Any adverse events which may related to MSC-EV infusion

  6 months after transplantation

Secondary Outcomes (3)

• Number of survived patients at 1 year after liver transplantation, according to the follow-up results.

  12 months

• Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.

  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.

  6 months after transplantation

Study Arms (2)

MSC-EVs group

EXPERIMENTAL

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-EVs

Non-MSC-EVs group

NO INTERVENTION

After liver transplantation, patients will receive postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.)

Interventions

MSC-EVs BIOLOGICAL

10 E10 MSC-EV particles per 100ml for a single dose. No prior HLA matching between MSC donors and recipients or liver donors

MSC-EVs group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 18-70 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;

You may not qualify if:

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

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

Third Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510630, China

Location

MeSH Terms

Conditions

Liver Failure

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Yang Yang, PHD, MD

  Third Affiliated Hospital, Sun Yat-Sen University, guangzhou, Guangdong, China

  STUDY DIRECTOR

Central Study Contacts

Jun Zheng, PHD, MD

CONTACT

020-85252113; zhengj67@mail2.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor of Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University

Study Record Dates

• First Submitted: February 9, 2025
• First Posted: February 13, 2025
• Study Start: April 1, 2025
• Primary Completion: March 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 13, 2025

Record last verified: 2025-02

Locations

CN (1)