Liver FailurePhase 1NCT06825572
MSC-EVs in Acute/ Acute-on-Chronic Liver Failure After Liver Transplantation
A Phase 1 study testing MSC-EVs in people with Liver Failure and Mesenchymal Stem Cell, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Failure, Mesenchymal Stem Cell, Extracellular Vesicles
- What is being tested?
- MSC-EVs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2025to 30 Sep 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- Past history of malignant disease
- Active uncontrolled infection;
- Combined transplantation
- EBV-negative;
- HIV or HCV positive;
- Retransplantation;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Third Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, 510630
Yang Yang, PHD, MD, 020-85252113, yysysu@163.com
Yang Yang, PHD, MD
About this study
Official title: Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute/Acute-on-Chronic Liver Failure After Liver Transplantationa：a Prospective, Randomized, Controlled Clinical Study
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.
Read the 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
- Being tested
- MSC-EVs
- Keywords
- MSC-EV, Liver transplantation, Liver failure
- Medical subject headings
- Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC-EVsBiological
10 E10 MSC-EV particles per 100ml for a single dose. No prior HLA matching between MSC donors and recipients or liver donors
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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.) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: 24 hours after injection
Aspartate aminotransferase (AST)
Collect clinical results reflecting liver function
Measured: 6 months after transplantation
Alanine aminotransferase (ALT)
Collect clinical results reflecting liver function
Measured: 6 months after transplantation
Bilirubin level
Collect clinical results reflecting liver function
Measured: 6 months after transplantation
International normalized ratio (INR)
Collect clinical results reflecting liver function
Measured: 6 months after transplantation
carbohydrate Compound antigen (GGT) level
Collect clinical results reflecting liver function
Measured: 6 months after transplantation
Adverse events
Any adverse events which may related to MSC-EV infusion
Measured: 6 months after transplantation
Secondary outcomes (3)
Number of survived patients at 1 year after liver transplantation, according to the follow-up results.
Patients who are surviving, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation
Measured: 12 months
Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.
Surviving patients with primary and functional grafts, as assessed by outpatient or telephone follow-up, at 1 year after liver transplantation.
Measured: 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.
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)
Measured: 6 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2025
- Study start1 Apr 2025 (estimated)
- Primary completion30 Mar 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun Zheng, Third Affiliated Hospital, Sun Yat-Sen University
- Investigators
- Yang Yang, PHD, MD, Study director, Third Affiliated Hospital, Sun Yat-Sen University, guangzhou, Guangdong, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06825572
- Sponsor's protocol ID
- MSC-EVs of ThirdSunYatSen
- Status last verified
- Feb 2025
- First submitted
- 9 Feb 2025
- Last updated
- 13 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute/Acute-on-Chronic Liver Failure After Liver Transplantationa：a Prospective, Randomized, Controlled Clinical Study
- ClinicalTrials.gov ID
- NCT06825572
- Acronym / sponsor ID
- MSC-EVs of ThirdSunYatSen
- Conditions
- Liver Failure, Mesenchymal Stem Cell, Extracellular Vesicles
- Keywords
- MSC-EV, Liver transplantation, Liver failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Apr 2025 (estimated)
- Primary completion
- 30 Mar 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 13 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSC-EVs group | Experimental | Biological: MSC-EVsAfter 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 |
| Non-MSC-EVs group | No intervention | –After liver transplantation, patients will receive postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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;
Key exclusion criteria (6 listed)
- Past history of malignant disease
- Active uncontrolled infection;
- Combined transplantation
- EBV-negative;
- HIV or HCV positive;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSC-EVs10 E10 MSC-EV particles per 100ml for a single dose. No prior HLA matching between MSC donors and recipients or liver donors | Biological | MSC-EVs group |
Primary outcome
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 .
Aspartate aminotransferase (AST)
Time frame: 6 months after transplantation
Collect clinical results reflecting liver function
Alanine aminotransferase (ALT)
Time frame: 6 months after transplantation
Collect clinical results reflecting liver function
Bilirubin level
Time frame: 6 months after transplantation
Collect clinical results reflecting liver function
International normalized ratio (INR)
Time frame: 6 months after transplantation
Collect clinical results reflecting liver function
carbohydrate Compound antigen (GGT) level
Time frame: 6 months after transplantation
Collect clinical results reflecting liver function
Adverse events
Time frame: 6 months after transplantation
Any adverse events which may related to MSC-EV infusion
3 secondary outcomes
Number of survived patients at 1 year after liver transplantation, according to the follow-up results.
Time frame: 12 months
Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.
Time frame: 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 after transplantation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yang Yang, PHD, MD study director
Third Affiliated Hospital, Sun Yat-Sen University, guangzhou, Guangdong, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MSC-EVs in people with Liver Failure and Mesenchymal Stem Cell, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jun Zheng, PHD, MD (020-85252113, zhengj67@mail2.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0. (time frame: 24 hours after injection). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025.