Decompensated CirrhosisPhase 2NCT05121870
Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis
A Phase 2 study testing UC-MSCs and Saline containing 1% Human serum albumin（solution without UC-MSCs） in people with Decompensated Cirrhosis, run by Beijing 302 Hospital at 5 sites in China.
Trial summary
Decompensated cirrhosis has a high overall mortality rate. There is a large unmet need for safe and alternative therapeutic potions. This clinical trial is to inspect the efficiency and safety of mesenchymal stem cells (MSCs) therapy for decompensated cirrhosis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Decompensated Cirrhosis
- What is being tested?
- UC-MSCs and Saline containing 1% Human serum albumin（solution without UC-MSCs）
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 5 sitesChina
- Study dates
- 1 Sep 2021to 31 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing to provide written informed consent;
- Aged 18 to 75 years (including 18 and 75 years), male or female;
- Patients diagnosed with decompensated liver cirrhosis based on clinical findings, laboratory tests, imaging findings and/or representative pathological findings (decompensated liver cirrhosis is defined as the occurrence of at least one serious complication, including esophageal and gastric varices bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis and other serious complications);
- Child-Turcotte-Pugh (CTP) score 7 to 12 points.
Who cannot join
- Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit.
- Uncontrolled severe infection within 2 weeks of screening.
- Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
- Patients with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HBV for less than 12 months.
- Patients with hepatitis C virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HCV for less than 12 months.
- Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
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- Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
- Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
- Severe jaundice (serum total bilirubin level ≥ 170μmol/L); Significant renal insufficiency (serum creatinine ≥ 1.2 times upper normal limit); Severe electrolyte abnormality (serum sodium level < 125 mmol/L); Severe leukopenia (white blood cell count < 1 × 10E9/L).
- Patients with biliary obstruction, hepatic vein, portal vein, splenic vein thrombosis and portal vein spongiosis.
- Patients with surgical history such as splenic cut-off flow and portal body shunt.
- Patients with confirmed or suspected malignancies.
- Patients with a prior history of major organ transplantation or complicated with significant disease of heart, lung, kidney, blood, endocrine and other systems.
- Drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
- HIV seropositivity.
- Those who have received blood transfusion or other blood products within 1 month prior to screening visit.
- Pregnancy, lactation or with recent fertility plan.
- Highly allergic or have a history of severe allergies.
- Participants in other clinical trials within the last 3 months.
- Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites, 5 recruiting
- Recruiting
Beijing 302 Hospital
Beijing
Lei Shi, MD,PhD, 86-10-66949623, shilei302@126.com
- Not yet recruiting
The First Hospital of Lanzhou University
Lanzhou, Gansu
Xun Li, lix@lzu.edu.cn
- Not yet recruiting
Hainan hospital of Chinese PLA General Hospital
Sanya, Hainan
Ya-Li Zhao, zhaoyl301@163.com
- Not yet recruiting
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, 200003
Wei-Fen Xie, MD, PhD, weifenxie@medmail.com.cn
- Not yet recruiting
Renmin Hospital of Wuhan University
Wuhan, Hubei
Ying-an Jiang, jiangya_cn@aliyun.com
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells Combined With Standard Therapy in Patients With Decompensated Cirrhosis
Decompensated cirrhosis has a high overall mortality rate. There is a large unmet need for safe and alternative therapeutic potions. This clinical trial is to inspect the efficiency and safety of mesenchymal stem cells (MSCs) therapy for decompensated cirrhosis.
Read the detailed description
Decompensated cirrhosis has a high overall mortality rate. Liver transplantation is still the most effective treatment for decompensated cirrhosis. However, the shortage of matched liver sources, high costs, and rejection after liver transplantation restrict the development of liver transplantation.
Mesenchymal stem cells (MSC) are a kind of pluripotent stem cells belonging to mesoderm, which mainly exist in connective tissue and organ interstitium. At present, MSC can be isolated and prepared from bone marrow, fat, synovium, bone, muscle, lung, liver, pancreas and amniotic fluid and umbilical cord blood . Due to its wide range of sources and self-proliferation and differentiation ability, MSCs have therapeutic potential for many diseases, including acute and chronic liver diseases.
In recent years, our team has carried out a series of clinical trials using umbilical cord-derived MSCs to treat patients with end-stage liver disease, decompensated cirrhosis, primary biliary cholangitis, and status after liver transplantation and found that MSCs therapy can significantly improve patient liver function, reduce post-transplantation rejection, reduce complications, improve quality of life, and improve survival. Other investigators have also found in clinical trials with MSCs from different sources that treatment with MSCs can improve MELD scores or liver function levels to varying degrees. However, some studies have found no significant difference between the treatment group and the control group, and MSCs may differentiate into hepatic stellate cells and have the risk of promoting liver fibrosis, it is believed that MSCs do not favor the improvement of liver function in these studies. Therefore, the therapeutic effects of MSCs need to be further validated by larger multicenter randomized controlled clinical trials.
The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 240 decompensated cirrhosis patients will be recruited in China.120 patients will receive i.v. transfusion 3 times of MSCs (6.0×10E7 cells per time) and the standard of care as the treated group. In addition, the 120 patients will receive placebo and standard of care as control group.
- Conditions
- Decompensated Cirrhosis
- Being tested
- UC-MSCs, Saline containing 1% Human serum albumin（solution without UC-MSCs）
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UC-MSCsBiological
3 does of UC-MSCs(6.0×10E7cells per time) intravenously at week 0, week 4, week 8.
Saline containing 1% Human serum albumin（solution without UC-MSCs）Biological
3 does of placebo intravenously at week 0, week 4, week 8.
| Study group | Role | What they receive |
|---|---|---|
| Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) | Experimental | standard of care (SOC) plus UC-MSCs Receives: Biological: UC-MSCs |
| Placebo | Placebo comparator | SOC plus placebo. Receives: Biological: Saline containing 1% Human serum albumin（solution without UC-MSCs） |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 24th week
The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology.
The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).
Measured: at 24th week
Secondary outcomes (13)
Change in MELD score from baseline to 48 weeks
Measured: up to 48 weeks
Incidence of each complication associated with decompensated cirrhosis
Measured: up to 48 weeks
liver transplant-free survival
Measured: up to 48 weeks
Incidence of liver failure
Measured: up to 48 weeks
plasma albumin (ALB)
Measured: up to 48 weeks
total bilirubin (TBIL)
Measured: up to 48 weeks
serum cholinesterase (CHE)
Measured: up to 48 weeks
prothrombin activity (PA)
Measured: up to 48 weeks
Child-Turcotte-Pugh (CTP) score
Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
Measured: up to 48 weeks
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Measured: up to 48 weeks
ChronicLiver Disease Questionnaire (CLDQ)
Measured: up to 48 weeks
Incidence of liver cancer
Measured: up to 48 weeks
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Measured: up to 48weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2021
- Study start1 Sep 2021
- Primary completion30 Jun 2023 (estimated)
- Study completion31 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 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
- Model description
- Randomized, double-blind, placebo-controlled, multicenter study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Changzheng Hospital, LanZhou University, Renmin Hospital of Wuhan University, Chinese PLA General Hospital, Vcanbio Cell and Gene Engineering Corp., Ltd.
- Responsible party
- Principal investigator, Fu-Sheng Wang, Beijing 302 Hospital
- Investigators
- Fu-Sheng Wang, MD, PhD, Study chair, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05121870
- Sponsor's protocol ID
- NCRC-ID202105
- Status last verified
- Nov 2021
- First submitted
- 17 Oct 2021
- Last updated
- 16 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells Combined With Standard Therapy in Patients With Decompensated Cirrhosis
- ClinicalTrials.gov ID
- NCT05121870
- Acronym / sponsor ID
- NCRC-ID202105
- Conditions
- Decompensated Cirrhosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Collaborators
- Shanghai Changzheng Hospital, LanZhou University, Renmin Hospital of Wuhan University, Chinese PLA General Hospital, Vcanbio Cell and Gene Engineering Corp., Ltd.
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 16 Nov 2021 (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 cirrhosis has a high overall mortality rate. There is a large unmet need for safe and alternative therapeutic potions. This clinical trial is to inspect the efficiency and safety of mesenchymal stem cells (MSCs) therapy for decompensated cirrhosis.
Detailed description
Decompensated cirrhosis has a high overall mortality rate. Liver transplantation is still the most effective treatment for decompensated cirrhosis. However, the shortage of matched liver sources, high costs, and rejection after liver transplantation restrict the development of liver transplantation.
Mesenchymal stem cells (MSC) are a kind of pluripotent stem cells belonging to mesoderm, which mainly exist in connective tissue and organ interstitium. At present, MSC can be isolated and prepared from bone marrow, fat, synovium, bone, muscle, lung, liver, pancreas and amniotic fluid and umbilical cord blood . Due to its wide range of sources and self-proliferation and differentiation ability, MSCs have therapeutic potential for many diseases, including acute and chronic liver diseases.
In recent years, our team has carried out a series of clinical trials using umbilical cord-derived MSCs to treat patients with end-stage liver disease, decompensated cirrhosis, primary biliary cholangitis, and status after liver transplantation and found that MSCs therapy can significantly improve patient liver function, reduce post-transplantation rejection, reduce complications, improve quality of life, and improve survival. Other investigators have also found in clinical trials with MSCs from different sources that treatment with MSCs can improve MELD scores or liver function levels to varying degrees. However, some studies have found no significant difference between the treatment group and the control group, and MSCs may differentiate into hepatic stellate cells and have the risk of promoting liver fibrosis, it is believed that MSCs do not favor the improvement of liver function in these studies. Therefore, the therapeutic effects of MSCs need to be further validated by larger multicenter randomized controlled clinical trials.
The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 240 decompensated cirrhosis patients will be recruited in China.120 patients will receive i.v. transfusion 3 times of MSCs (6.0×10E7 cells per time) and the standard of care as the treated group. In addition, the 120 patients will receive placebo and standard of care as control group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled, multicenter study
| Arm | Type | Receives |
|---|---|---|
| Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) | Experimental | Biological: UC-MSCsstandard of care (SOC) plus UC-MSCs |
| Placebo | Placebo comparator | Biological: Saline containing 1% Human serum albumin（solution without UC-MSCs）SOC plus placebo. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Willing to provide written informed consent;
- Aged 18 to 75 years (including 18 and 75 years), male or female;
- Patients diagnosed with decompensated liver cirrhosis based on clinical findings, laboratory tests, imaging findings and/or representative pathological findings (decompensated liver cirrhosis is defined as the occurrence of at least one serious complication, including esophageal and gastric varices bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis and other serious complications);
- Child-Turcotte-Pugh (CTP) score 7 to 12 points.
Key exclusion criteria (20 listed)
- Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit.
- Uncontrolled severe infection within 2 weeks of screening.
- Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
- Patients with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HBV for less than 12 months.
- Patients with hepatitis C virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HCV for less than 12 months.
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 |
|---|---|---|
| UC-MSCs3 does of UC-MSCs(6.0×10E7cells per time) intravenously at week 0, week 4, week 8. | Biological | Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) |
| Saline containing 1% Human serum albumin（solution without UC-MSCs）3 does of placebo intravenously at week 0, week 4, week 8. | Biological | Placebo |
Primary outcome
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 24th week
Time frame: at 24th week
The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology. The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).
13 secondary outcomes
Change in MELD score from baseline to 48 weeks
Time frame: up to 48 weeks
Incidence of each complication associated with decompensated cirrhosis
Time frame: up to 48 weeks
liver transplant-free survival
Time frame: up to 48 weeks
Incidence of liver failure
Time frame: up to 48 weeks
plasma albumin (ALB)
Time frame: up to 48 weeks
total bilirubin (TBIL)
Time frame: up to 48 weeks
serum cholinesterase (CHE)
Time frame: up to 48 weeks
prothrombin activity (PA)
Time frame: up to 48 weeks
Child-Turcotte-Pugh (CTP) score
Time frame: up to 48 weeks
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Time frame: up to 48 weeks
ChronicLiver Disease Questionnaire (CLDQ)
Time frame: up to 48 weeks
Incidence of liver cancer
Time frame: up to 48 weeks
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Time frame: up to 48weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2021.
- Individual participant dataSharing planned: Yes. After approval from the steering committee and the Human Genetic Resources Administration of China, this trial data can be shared with qualifying researchers who submit a proposal with a valuable research question. A contract should be signed.
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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, MD, PhD study chair
Beijing 302 Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing UC-MSCs and Saline containing 1% Human serum albumin（solution without UC-MSCs） in people with Decompensated Cirrhosis, run by Beijing 302 Hospital at 5 sites 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 20 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 16 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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. Some participants in this study may receive a placebo. 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 Lei Shi, MD,PhD (86-10-66949623, shilei302@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 24th week (time frame: at 24th week). 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 16 Nov 2021.