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

NCT05881668 | Withdrawn Phase 1

• 1 other identifier: MSC-EV of ThirdSunYatSen
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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, Acute on Chronic

Keywords

MSC-EV; Acute-on-chronic liver failure; Liver transplantation

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

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

Study Arms (2)

MSC-EV 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-EV

Non-MSC-EV group

NO INTERVENTION

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

Interventions

MSC-EV 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-EV group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;

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

Related Publications (3)

• Detry O, Vandermeulen M, Delbouille MH, Somja J, Bletard N, Briquet A, Lechanteur C, Giet O, Baudoux E, Hannon M, Baron F, Beguin Y. Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study. J Hepatol. 2017 Jul;67(1):47-55. doi: 10.1016/j.jhep.2017.03.001. Epub 2017 Mar 9.

  PMID: 28284916 BACKGROUND

• Lin BL, Chen JF, Qiu WH, Wang KW, Xie DY, Chen XY, Liu QL, Peng L, Li JG, Mei YY, Weng WZ, Peng YW, Cao HJ, Xie JQ, Xie SB, Xiang AP, Gao ZL. Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial. Hepatology. 2017 Jul;66(1):209-219. doi: 10.1002/hep.29189. Epub 2017 May 27.

  PMID: 28370357 BACKGROUND

• Psaraki A, Ntari L, Karakostas C, Korrou-Karava D, Roubelakis MG. Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases. Hepatology. 2022 Jun;75(6):1590-1603. doi: 10.1002/hep.32129. Epub 2021 Nov 27.

  PMID: 34449901 BACKGROUND

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Yang Yang, PHD, MD

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

  PRINCIPAL INVESTIGATOR

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: Head 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: May 8, 2023
• First Posted: May 31, 2023
• Study Start: September 30, 2023
• Primary Completion: September 30, 2024
• Study Completion: April 30, 2025
• Last Updated: October 12, 2023

Record last verified: 2023-10

Locations

CN (1)