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

NCT ID: NCT06825572

Last Updated: 2025-02-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-09-30

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.

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.

Conditions

Liver Failure; Mesenchymal Stem Cell; Extracellular Vesicles

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MSC-EVs 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

Group Type: EXPERIMENTAL

MSC-EVs

Intervention Type: BIOLOGICAL

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

Non-MSC-EVs group

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

MSC-EVs

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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;

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Jun Zheng

Doctor of Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yang Yang, PHD, MD

Role: STUDY_DIRECTOR

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

Locations

Third Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Jun Zheng, PHD, MD

Role: CONTACT

zhengj67@mail2.sysu.edu.cn

020-85252113

Facility Contacts

Yang Yang, PHD, MD

Role: primary

yysysu@163.com

020-85252113

Other Identifiers

MSC-EVs of ThirdSunYatSen

Identifier Type: -

Identifier Source: org_study_id