Acute-On-Chronic Liver FailurePhase 1/2NCT05940610
The Safety and Efficacy of MSC-EVs in Acute/Acute-on-Chronic Liver Failure
A Phase 1/2 study testing MSC-EVs in people with Acute-On-Chronic Liver Failure and Acute Liver Failure, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
Trial summary
Acute-on-chronic liver failure (ACLF) 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，while acute liver failure (ALF) refers to a… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute-On-Chronic Liver Failure, Acute Liver Failure
- 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
- 0 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2023to 1 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged 18-65 years old;
- 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; Acute liver failure-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.
- Total bilirubin (TBil) ≥ 171umolL or daily increase ≥17.1umol/L;
- Prothrombin activity (PTA) between 20% and 40% (or INR between 1.5 and 2.6);
- No hepatic encephalopathy, or encephalopathy below grade II (including grade II);
Who cannot join
- Patients with primary or metastatic liver cancer
- Severe active bleeding or diffuse intravascular coagulation
- Patients who are allergic to blood products or drugs used in treatment, such as plasma, heparin and protamine;
- MELD score >30
- Other serious disease including heart disease, lung disease, blood disease, autoimmune disease, diabetes, active uncontrolled infection,etc.
Trial locations and contacts
1 site in 1 country.
China1 site
Third Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, 510630
About this study
Official title: The Safety and Efficacy of Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute/Acute-on-Chronic Liver Failure：a Prospective, Randomized, Controlled Clinical Study
Acute-on-chronic liver failure (ACLF) 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，while 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. Liver transplantation is the only curative treatment for this type of end-stage liver disease, but the rapid disease progression and lack of donors limit its application. 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. It has been confirmed in previous studies that infusion of allogeneic MSCs is safe and convenient for patients with ACLF and improve liver function and decrease the incidence of severe infections. Compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) 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 efficacy of MSC-EVs in ACLF/ALF .
Read the detailed description
In the MSC-EV group (experimental group), onthe basis of standard medical treatment, 10 patients will receive a single injection of MSC-EV . In the non-MSC-EV group (control group), 10 patients will not receive MSC-EV therapy but standard medical treatment. The standard medical treatment iclude nutritional supplementation, administration of human serum albumin and fresh frozen plasma, anti-viral therapy (if hepatitis virus-related ACLF/ALF), liver protective treatment and other appropriate treatment for complications.
The outcome of the experimental group will be compared with that of similar control patients who will not receive MSC-EV. Both of the two groups will receive standard medical treatment. Patients participated in the experimental cohort will be infused with a single dose of 10 E10 MSC-EV particles per 100ml, when they are inpatient.
- Being tested
- MSC-EVs
- Keywords
- MSC-EVs, Acute-on-chronic liver failure, Acute liver failure, Liver transplantation
- Medical subject headings
- Acute-On-Chronic Liver Failure, Liver Failure, Acute
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. Once a week for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| MSC-EV group | Experimental | On the basis of standard medical treatment, an additional injection of MSC-EVs will be received by participants once a week for 4 weeks while hospitalized. Receives: Biological: MSC-EVs |
| Non-MSC-EV group | No intervention | In the non-MSC-EV group, patients will receive standard medical treatment and 100ml saline as a control. |
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 first rejection
Alanine aminotransferase (ALT)
Collect clinical results reflecting liver function
Measured: 6 months after first rejection
Bilirubin level
Collect clinical results reflecting liver function
Measured: 6 months after first rejection
International normalized ratio (INR)
Collect clinical results reflecting liver function
Measured: 6 months after first rejection
Carbohydrate Compound antigen (GGT) level
Collect clinical results reflecting liver function
Measured: 6 months after first rejection
Adverse events
Any adverse events which may related to MSC-EV infusion
Measured: 6 months after first rejection
Secondary outcomes (2)
Number of survived patients at 1 year, according to the follow-up results
Patients who are surviving, as assessed by outpatient or telephone follow-up, at 1 year after rejection
Measured: 12 months
Proportion of immune cell subsets from biopsy or blood samples ,at months 1-6 after infusion.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2023
- Study start1 Sep 2023 (estimated)
- Primary completion30 Sep 2024 (estimated)
- Study completion1 Oct 2025 (estimated)
Why it stopped: The supply of msc-ev has been delayed and approval by the Ethics committee will take some time.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute-On-Chronic 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yang Yang, Third Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05940610
- Sponsor's protocol ID
- MSC-EVs-2 of ThirdSunYatSen
- Status last verified
- Oct 2023
- First submitted
- 2 Jul 2023
- Last updated
- 12 Oct 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Efficacy of Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute/Acute-on-Chronic Liver Failure：a Prospective, Randomized, Controlled Clinical Study
- ClinicalTrials.gov ID
- NCT05940610
- Acronym / sponsor ID
- MSC-EVs-2 of ThirdSunYatSen
- Keywords
- MSC-EVs, Acute-on-chronic liver failure, Acute liver failure, Liver transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The supply of msc-ev has been delayed and approval by the Ethics committee will take some time.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Sep 2023 (estimated)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 11 Jul 2023 (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-on-chronic liver failure (ACLF) 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，while 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. Liver transplantation is the only curative treatment for this type of end-stage liver disease, but the rapid disease progression and lack of donors limit its application. 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. It has been confirmed in previous studies that infusion of allogeneic MSCs is safe and convenient for patients with ACLF and improve liver function and decrease the incidence of severe infections. Compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) 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 efficacy of MSC-EVs in ACLF/ALF .
Detailed description
In the MSC-EV group (experimental group), onthe basis of standard medical treatment, 10 patients will receive a single injection of MSC-EV . In the non-MSC-EV group (control group), 10 patients will not receive MSC-EV therapy but standard medical treatment. The standard medical treatment iclude nutritional supplementation, administration of human serum albumin and fresh frozen plasma, anti-viral therapy (if hepatitis virus-related ACLF/ALF), liver protective treatment and other appropriate treatment for complications.
The outcome of the experimental group will be compared with that of similar control patients who will not receive MSC-EV. Both of the two groups will receive standard medical treatment. Patients participated in the experimental cohort will be infused with a single dose of 10 E10 MSC-EV particles per 100ml, when they are inpatient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSC-EV group | Experimental | Biological: MSC-EVsOn the basis of standard medical treatment, an additional injection of MSC-EVs will be received by participants once a week for 4 weeks while hospitalized. |
| Non-MSC-EV group | No intervention | –In the non-MSC-EV group, patients will receive standard medical treatment and 100ml saline as a control. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- aged 18-65 years old;
- 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; Acute liver failure-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.
- Total bilirubin (TBil) ≥ 171umolL or daily increase ≥17.1umol/L;
- Prothrombin activity (PTA) between 20% and 40% (or INR between 1.5 and 2.6);
- No hepatic encephalopathy, or encephalopathy below grade II (including grade II);
Key exclusion criteria (5 listed)
- Patients with primary or metastatic liver cancer
- Severe active bleeding or diffuse intravascular coagulation
- Patients who are allergic to blood products or drugs used in treatment, such as plasma, heparin and protamine;
- MELD score >30
- Other serious disease including heart disease, lung disease, blood disease, autoimmune disease, diabetes, active uncontrolled infection,etc.
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. Once a week for 4 weeks. | Biological | MSC-EV 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 first rejection
Collect clinical results reflecting liver function
Alanine aminotransferase (ALT)
Time frame: 6 months after first rejection
Collect clinical results reflecting liver function
Bilirubin level
Time frame: 6 months after first rejection
Collect clinical results reflecting liver function
International normalized ratio (INR)
Time frame: 6 months after first rejection
Collect clinical results reflecting liver function
Carbohydrate Compound antigen (GGT) level
Time frame: 6 months after first rejection
Collect clinical results reflecting liver function
Adverse events
Time frame: 6 months after first rejection
Any adverse events which may related to MSC-EV infusion
2 secondary outcomes
Number of survived patients at 1 year, according to the follow-up results
Time frame: 12 months
Proportion of immune cell subsets from biopsy or blood samples ,at months 1-6 after infusion.
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MSC-EVs in people with Acute-On-Chronic Liver Failure and Acute Liver Failure, 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 5 inclusion and 5 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: withdrawn, as of the sponsor's last update on 12 Oct 2023. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. 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 12 Oct 2023.