Decompensated CirrhosisPhase 2NCT05224960
Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-2)
A Phase 2 study testing UC-MSCs in people with Decompensated Cirrhosis, run by Beijing 302 Hospital at 7 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 7 sitesChina
- Study dates
- 27 Jun 2024to 20 Jun 2027
- Phase
- Phase 2
- 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 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);
- The Model for End-stage Liver Disease (MELD) score 15 to 30 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.
- 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, or hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
- 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, or hepatitis C virus (HCV) RNA ≥ detection limit at the time of screening (except HCV RNA< detection limit without any antiviral treatment).
- Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
- Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
Show all 21Show fewer
- Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
- 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, or portal vein spongiosis.
- Patients with surgical history such as splenic cut-off flow.
- Patients with malignant tumors within 5 years, except those with basal cell carcinoma, squamous cell carcinoma and/or carcinoma in situ who had received curative treatment and curative resection.
- 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.
- Against the human immunodeficiency virus antibody (Anti - HIV) or syphilis antibody test results were positive.
- Pregnancy, lactation or with recent fertility plan during the test and 6 months after the test.
- Highly allergic, or have a history of severe allergies, known severe allergies to the investigational drug or any of the excipients.
- History of pulmonary embolism.
- Patients who had previously received stem cell therapy or were intolerant to cell therapy.
- The proposed line of liver transplants within three months.
- 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
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
China7 sites, 7 recruiting
- Recruiting
Beijing 302 Hospital
Beijing
Lei Shi, MD, PhD, 86-10-66949623, shilei302@126.com
- Not yet recruiting
Third Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong
Qi Zhang, zhangq27@mail.sysu.edu.cn
- Not yet recruiting
Xinjiang Kashi Area Number 1 Hospital
Kashgar, Xinjiang
Fei Xiao, xiaof35@sysu.edu.cn
- Not yet recruiting
The First Hospital of Lanzhou University
Lanzhou, Gansu
Xun Li, lix@lzu.edu.cn
- Recruiting
Hainan hospital of Chinese PLA General Hospital
Sanya, Hainan
Ya-Li Zhao, zhaoyl301@163.com
- Recruiting
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, 200003
Wei-Fen Xie, MD, PhD, weifenxie@medmail.com.cn
- Not yet recruiting
Jin Yin-tan Hospital
Wuhan, Hubei
Chaolin Huang, 88071718@qq.com
About this study
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Decompensated Cirrhosis Patients(MSC-DLC-2)
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, muliticenter, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 140 decompensated cirrhosis patients will be recruited in China. 70 patients will receive i.v. transfusion 3 times of MSCs and the standard of care as the treated group. In addition, the 70 patients will receive placebo and standard of care as control group.
- Conditions
- Decompensated Cirrhosis
- Being tested
- UC-MSCs, Placebo(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 doses of UC-MSCs intravenously at day 1, day 8, day 15.
Placebo(solution without UC-MSCs)Biological
3 doses of placebo intravenously at day 1, day 8, day 15.
| Study group | Role | What they receive |
|---|---|---|
| Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) | Experimental | UC-MSCs plus standard of care (SOC). Receives: Biological: UC-MSCs |
| Placebo | Placebo comparator | Placebo plus SOC. Receives: Biological: Placebo(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 28th day
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.
Measured: Baseline, 28th day
Secondary outcomes (23)
Change in MELD score from baseline to 24 months
Measured: up to 24 months
Incidence of each complication associated with decompensated cirrhosis
Measured: up to 24 months
Liver transplant-free survival
Measured: month 12 and 24
Incidence of liver failure
Measured: month 12 and 24
plasma albumin (ALB)
Measured: up to 24 months
plasma prealbumin (PALB)
Measured: up to 24 months
total bilirubin (TBIL)
Measured: up to 24 months
serum cholinesterase (CHE)
Measured: up to 24 months
prothrombin activity (PA)
Measured: up to 24 months
Child-Turcotte-Pugh (CTP) score
Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
Measured: up to 24 months
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Measured: up to 24 months
ChronicLiver Disease Questionnaire (CLDQ)
Measured: up to 24 months
Incidence of liver cancer
Measured: up to 24 months
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Measured: up to 24 months
Alanine Aminotransferase (ALT)
Measured: up to 24 months
Aspartate Aminotransferase (AST)
Measured: up to 24 months
Alkaline Phosphatase (ALP)
Measured: up to 24 months
Gamma-Glutamyl transferase (GGT)
Measured: up to 24 months
plasma ammonia
Measured: up to 24 months
international normalized ratio (INR)
Measured: up to 24 months
creatinine （Cr）
Measured: up to 24 months
Prothrombin time (PT)
Measured: up to 24 months
Liver transplant-free survival rate
Measured: month 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start27 Jun 2024
- Primary completion27 Jun 2025 (estimated)
- Study completion20 Jun 2027 (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
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Chinese PLA General Hospital, Shanghai Changzheng Hospital, LanZhou University, Jin Yin-tan Hospital, Hainan General Hospital, Vcanbio Cell and Gene Engineering Corp., Ltd., Third Affiliated Hospital, Sun Yat-Sen University, Xinjiang Kashi Area Number 1 Hospital
- 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
- NCT05224960
- Sponsor's protocol ID
- MSC-DLC-2
- Status last verified
- Oct 2024
- First submitted
- 26 Jan 2022
- Last updated
- 18 Oct 2024
- 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 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Decompensated Cirrhosis Patients(MSC-DLC-2)
- ClinicalTrials.gov ID
- NCT05224960
- Acronym / sponsor ID
- MSC-DLC-2
- Conditions
- Decompensated Cirrhosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Collaborators
- Chinese PLA General Hospital, Shanghai Changzheng Hospital, LanZhou University, Jin Yin-tan Hospital, Hainan General Hospital, Vcanbio Cell and Gene Engineering Corp., Ltd., Third Affiliated Hospital, Sun Yat-Sen University, Xinjiang Kashi Area Number 1 Hospital
- Study start
- 27 Jun 2024 (actual)
- Primary completion
- 27 Jun 2025 (estimated)
- Study completion
- 20 Jun 2027 (estimated)
- First posted
- 4 Feb 2022 (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, muliticenter, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 140 decompensated cirrhosis patients will be recruited in China. 70 patients will receive i.v. transfusion 3 times of MSCs and the standard of care as the treated group. In addition, the 70 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-MSCsUC-MSCs plus standard of care (SOC). |
| Placebo | Placebo comparator | Biological: Placebo(solution without UC-MSCs)Placebo plus SOC. |
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);
- The Model for End-stage Liver Disease (MELD) score 15 to 30 points.
Key exclusion criteria (21 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.
- 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, or hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
- 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, or hepatitis C virus (HCV) RNA ≥ detection limit at the time of screening (except HCV RNA< detection limit without any antiviral treatment).
- Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 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 doses of UC-MSCs intravenously at day 1, day 8, day 15. | Biological | Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs) |
| Placebo(solution without UC-MSCs)3 doses of placebo intravenously at day 1, day 8, day 15. | Biological | Placebo |
Primary outcome
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
Time frame: Baseline, 28th day
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.
23 secondary outcomes
Change in MELD score from baseline to 24 months
Time frame: up to 24 months
Incidence of each complication associated with decompensated cirrhosis
Time frame: up to 24 months
Liver transplant-free survival
Time frame: month 12 and 24
Incidence of liver failure
Time frame: month 12 and 24
plasma albumin (ALB)
Time frame: up to 24 months
plasma prealbumin (PALB)
Time frame: up to 24 months
total bilirubin (TBIL)
Time frame: up to 24 months
serum cholinesterase (CHE)
Time frame: up to 24 months
prothrombin activity (PA)
Time frame: up to 24 months
Child-Turcotte-Pugh (CTP) score
Time frame: up to 24 months
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Time frame: up to 24 months
ChronicLiver Disease Questionnaire (CLDQ)
Time frame: up to 24 months
Incidence of liver cancer
Time frame: up to 24 months
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Time frame: up to 24 months
Alanine Aminotransferase (ALT)
Time frame: up to 24 months
Aspartate Aminotransferase (AST)
Time frame: up to 24 months
Alkaline Phosphatase (ALP)
Time frame: up to 24 months
Gamma-Glutamyl transferase (GGT)
Time frame: up to 24 months
plasma ammonia
Time frame: up to 24 months
international normalized ratio (INR)
Time frame: up to 24 months
creatinine （Cr）
Time frame: up to 24 months
Prothrombin time (PT)
Time frame: up to 24 months
Liver transplant-free survival rate
Time frame: month 12 and 24
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 18 Oct 2024.
- 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.
Fu-Sheng Wang, MD, PhD study chair
Beijing 302 Hospital
7 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 in people with Decompensated Cirrhosis, run by Beijing 302 Hospital at 7 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 21 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: looking for participants now, as of the sponsor's last update on 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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?
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 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 28th day (time frame: Baseline, 28th day). 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 18 Oct 2024.