Decompensated Liver CirrhosisPhase 2NCT03945487
Mesenchymal Stem Cells Treatment for Decompensated Liver Cirrhosis
A Phase 2 study testing umbilical cord-derived mesenchymal stem cell and Comprehensive treatment in people with Decompensated Liver Cirrhosis, run by Beijing 302 Hospital at 1 site in China.
Trial summary
Decompensated liver cirrhosis is a life-threatening chronic liver disease with high mortality. Liver transplantation is the only option that can improve the survival of these patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Decompensated Liver Cirrhosis
- What is being tested?
- umbilical cord-derived mesenchymal stem cell and Comprehensive treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 20 May 2019to 30 Dec 2023
- Phase
- Phase 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-69 years;
- Decompensated liver cirrhosis (manifestations including gastrointestinal bleeding, hepatic encephalopathy, and ascites, based on previously stable cirrhosis);
- Positive testing for serum hepatitis B surface antigen (HBsAg) for more than 6 months (chronic hepatitis B patients);
- Written consent.
Who cannot join
- Hepatocellular carcinoma or other malignancies;
- Liver cirrhosis caused by other reasons, such as autoimmune diseases, alcocal, drugs and so on;
- Pregnant women;
- The presence of other vital organ severe dysfunction;
- Participate in other studies;
- Lack of a supportive family;
- Refusal to sign the informed consent form.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing 302 Hospital
Beijing, 100039
Ming Shi
About this study
Official title: Safety and Efficacy of Human Unbilical Cord Derived-mesenchymal Stem Cells Treatment for Patients With Decompensated Liver Cirrhosis
Decompensated liver cirrhosis is a life-threatening chronic liver disease with high mortality. Liver transplantation is the only option that can improve the survival of these patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists, multiple complications, and high cost. Our and other previous studies have demonstrated that marrow bone-derived mesenchymal stem cells (BM-MSC) or unbilical cord derived MSC (UC-MSC) infusion is clinically safe and could improve liver function in patients with decompensated liver cirrhosis. However, the long-term outcomes of MSC infusion have not been reported until now. This prospective and randomized controlled study examined the longer-term safety and efficacy of UC-MSC in patients with decompensated liver cirrhosis.
Read the detailed description
Liver cirrhosis represents a late stage of progressive hepatic fibrosis characterized by the formation and accumulation of an extracellular matrix, which leads to the progressive distortion of the hepatic architecture. In China, the most important cause of liver cirrhosis is chronic hepatitis B virus (HBV) infection. Liver cirrhosis usually progresses irreversibly into advanced stage, such as a decompensated stage which is characterized by a series of clinical manifestations, including ascites, variceal hemorrhage, and hepatic encephalopathy with high mortality. Liver transplantation is the only option that can improve the survival of these decompensated liver cirrhosis patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists, multiple complications, and high cost. Therefore, it is urgent to find a safe and effective therapeutic approach to decompensated liver cirrhosis.
Animal models have shown that bone marrow-derived MSC (BM-MSC) can ameliorate liver fibrosis and reverse fulminant hepatic failure. In clinical, autologous BM-MSC have significantly improved liver function in patients with liver cirrhosis. A recent research also found that autologous BM-MSC therapy safely improved histological fibrosis and liver function in patients with alcoholic cirrhosis. Allogeneic MSC therapy, such as umbilical cord-derived MSC (UC-MSC), have shown to be safe and beneficial for the patients with liver cirrhosis caused by autoimmune diseases. Our previous studies showed that infusions of UC-MSC significantly improved liver function in decompensated liver cirrhosis and primary biliary cirrhosis (PBC) patients and increased the survival rate in acute-on-chronic liver failure (ACLF) patients. However, the single-center clinical study, the relative small size of the patient cohorts, absence of evaluation on long-term efficacy prevent firm conclusions being made with regard to the safety and efficacy of this treatment in liver diseases.
The purpose of this study is to investigate whether and how UC-MSC can improve the liver function, and the incidence of serious complications in patients with decompensated liver cirrhosis through a multi-center clinical study.
- Conditions
- Decompensated Liver Cirrhosis
- Being tested
- umbilical cord-derived mesenchymal stem cell, Comprehensive treatment
- Keywords
- liver cirrhosis, mesenchymal stem cells, safety, liver function
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
umbilical cord-derived mesenchymal stem cellBiological
Taken a dose of 1.0*10E6 UC-MSC/kg body weight intravenously three times at 3-week intervals, in addition to comprehensive treatment.
Comprehensive treatmentOther
- All patients received anti-HBV treatment with NAs (entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)).
- Strategies based on targeting abnormalities in gut-liver axis by antibiotic administration (i.e. rifaximin), improving the disturbed systemic circulatory function (i.e. longterm albumin administration), decreasing the inflammatory state (i.e. statins), and reducing portal hypertension (i.e. beta-blockers).
| Study group | Role | What they receive |
|---|---|---|
| Comprehensive treatment plus UC-MSC treatment | Experimental | Not described Receives: Biological: umbilical cord-derived mesenchymal stem cell |
| Comprehensive treatment | Other | Not described Receives: Other: Comprehensive treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver function
including the levels of albumin [ALB], prothrombin activity [PTA], total bilirubin [TBIL, and cholinesterase [CHE].
Measured: 96 weeks
The incidence of serious complications
including infection, gastrointestinal bleeding, encephalopathy, and hepatorenal syndrome.
Measured: 96 weeks
Secondary outcomes (3)
The incidence of adverse events
e.g. fever, allergy, rash, infection
Measured: 96 weeks
Disease-free survival time
The length of survival time after first UC-MSC treatment for the patient during the follow-up period.
Measured: 96 weeks
Incidence of hepatocellular carcinoma (HCC) events
HCC deveopled in the patient during the follow-up period.
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2019
- Study start20 May 2019 (estimated)
- Primary completion30 Dec 2021 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Decompensated Liver CirrhosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fu-Sheng Wang, Beijing 302 Hospital
- Investigators
- Fu-Sheng Wang, Study chair, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03945487
- Sponsor's protocol ID
- Beijing302-011
- Status last verified
- May 2019
- First submitted
- 9 May 2019
- Last updated
- 10 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Human Unbilical Cord Derived-mesenchymal Stem Cells Treatment for Patients With Decompensated Liver Cirrhosis
- ClinicalTrials.gov ID
- NCT03945487
- Acronym / sponsor ID
- Beijing302-011
- Conditions
- Decompensated Liver Cirrhosis
- Keywords
- liver cirrhosis, mesenchymal stem cells, safety, liver function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Study start
- 20 May 2019 (estimated)
- Primary completion
- 30 Dec 2021 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 10 May 2019 (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.
Decompensated liver cirrhosis is a life-threatening chronic liver disease with high mortality. Liver transplantation is the only option that can improve the survival of these patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists, multiple complications, and high cost. Our and other previous studies have demonstrated that marrow bone-derived mesenchymal stem cells (BM-MSC) or unbilical cord derived MSC (UC-MSC) infusion is clinically safe and could improve liver function in patients with decompensated liver cirrhosis. However, the long-term outcomes of MSC infusion have not been reported until now. This prospective and randomized controlled study examined the longer-term safety and efficacy of UC-MSC in patients with decompensated liver cirrhosis.
Detailed description
Liver cirrhosis represents a late stage of progressive hepatic fibrosis characterized by the formation and accumulation of an extracellular matrix, which leads to the progressive distortion of the hepatic architecture. In China, the most important cause of liver cirrhosis is chronic hepatitis B virus (HBV) infection. Liver cirrhosis usually progresses irreversibly into advanced stage, such as a decompensated stage which is characterized by a series of clinical manifestations, including ascites, variceal hemorrhage, and hepatic encephalopathy with high mortality. Liver transplantation is the only option that can improve the survival of these decompensated liver cirrhosis patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists, multiple complications, and high cost. Therefore, it is urgent to find a safe and effective therapeutic approach to decompensated liver cirrhosis.
Animal models have shown that bone marrow-derived MSC (BM-MSC) can ameliorate liver fibrosis and reverse fulminant hepatic failure. In clinical, autologous BM-MSC have significantly improved liver function in patients with liver cirrhosis. A recent research also found that autologous BM-MSC therapy safely improved histological fibrosis and liver function in patients with alcoholic cirrhosis. Allogeneic MSC therapy, such as umbilical cord-derived MSC (UC-MSC), have shown to be safe and beneficial for the patients with liver cirrhosis caused by autoimmune diseases. Our previous studies showed that infusions of UC-MSC significantly improved liver function in decompensated liver cirrhosis and primary biliary cirrhosis (PBC) patients and increased the survival rate in acute-on-chronic liver failure (ACLF) patients. However, the single-center clinical study, the relative small size of the patient cohorts, absence of evaluation on long-term efficacy prevent firm conclusions being made with regard to the safety and efficacy of this treatment in liver diseases.
The purpose of this study is to investigate whether and how UC-MSC can improve the liver function, and the incidence of serious complications in patients with decompensated liver cirrhosis through a multi-center clinical study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Comprehensive treatment plus UC-MSC treatment | Experimental | Biological: umbilical cord-derived mesenchymal stem cell |
| Comprehensive treatment | Other | Other: Comprehensive treatment |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-69 years;
- Decompensated liver cirrhosis (manifestations including gastrointestinal bleeding, hepatic encephalopathy, and ascites, based on previously stable cirrhosis);
- Positive testing for serum hepatitis B surface antigen (HBsAg) for more than 6 months (chronic hepatitis B patients);
- Written consent.
Key exclusion criteria (7 listed)
- Hepatocellular carcinoma or other malignancies;
- Liver cirrhosis caused by other reasons, such as autoimmune diseases, alcocal, drugs and so on;
- Pregnant women;
- The presence of other vital organ severe dysfunction;
- Participate in other studies;
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 |
|---|---|---|
| umbilical cord-derived mesenchymal stem cellTaken a dose of 1.0*10E6 UC-MSC/kg body weight intravenously three times at 3-week intervals, in addition to comprehensive treatment. | Biological | Comprehensive treatment plus UC-MSC treatment |
| Comprehensive treatment1. All patients received anti-HBV treatment with NAs (entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)). 2. Strategies based on targeting abnormalities in gut-liver axis by antibiotic administration (i.e. rifaximin), improving the disturbed systemic circulatory function (i.e. longterm albumin administration), decreasing the inflammatory state (i.e. statins), and reducing portal hypertension (i.e. beta-blockers). | Other | Comprehensive treatment |
Primary outcome
Liver function
Time frame: 96 weeks
including the levels of albumin [ALB], prothrombin activity [PTA], total bilirubin [TBIL, and cholinesterase [CHE].
The incidence of serious complications
Time frame: 96 weeks
including infection, gastrointestinal bleeding, encephalopathy, and hepatorenal syndrome.
3 secondary outcomes
The incidence of adverse events
Time frame: 96 weeks
Disease-free survival time
Time frame: 96 weeks
Incidence of hepatocellular carcinoma (HCC) events
Time frame: 96 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2019.
- Individual participant dataSharing planned: No
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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.
Fu-Sheng Wang study chair
Beijing 302 Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing umbilical cord-derived mesenchymal stem cell and Comprehensive treatment in people with Decompensated Liver Cirrhosis, run by Beijing 302 Hospital 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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 10 May 2019. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ming Shi (86-10-63879735, shiming302@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver function (time frame: 96 weeks). The study lists 2 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 10 May 2019.