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Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-2)

Primary Purpose

Decompensated Cirrhosis

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
UC-MSCs
Placebo(solution without UC-MSCs)
Sponsored by
Beijing 302 Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Decompensated Cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Willing to provide written informed consent;
  2. Aged 18 to 75 years (including 18 and 75 years), male or female;
  3. 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);
  4. Child-Turcotte-Pugh (CTP) score 7 to 12 points.

Exclusion Criteria:

  1. Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit.
  2. Uncontrolled severe infection within 2 weeks of screening.
  3. Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
  4. 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.
  5. 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.
  6. Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
  7. Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
  8. Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
  9. 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).
  10. Patients with biliary obstruction, hepatic vein, portal vein, splenic vein thrombosis and portal vein spongiosis.
  11. Patients with surgical history such as splenic cut-off flow and portal body shunt.
  12. Patients with confirmed or suspected malignancies.
  13. Patients with a prior history of major organ transplantation or complicated with significant disease of heart, lung, kidney, blood, endocrine and other systems.
  14. Drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
  15. HIV seropositivity.
  16. Those who have received blood transfusion or other blood products within 1 month prior to screening visit.
  17. Pregnancy, lactation or with recent fertility plan.
  18. Highly allergic or have a history of severe allergies.
  19. Participants in other clinical trials within the last 3 months.
  20. Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.

Sites / Locations

  • The First Hospital of Lanzhou University
  • Hainan hospital of Chinese PLA General Hospital
  • Jin Yin-tan hospital
  • Renmin Hospital of Wuhan University
  • Shanghai Changzheng Hospital
  • Beijing 302 Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)

Placebo

Arm Description

UC-MSCs plus standard of care (SOC).

Placebo plus SOC.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in MELD score from baseline to 96 weeks
Incidence of each complication associated with decompensated cirrhosis
liver transplant-free survival
Incidence of liver failure
plasma albumin (ALB)
plasma prealbumin (PALB)
total bilirubin (TBIL)
serum cholinesterase (CHE)
prothrombin activity (PA)
Child-Turcotte-Pugh (CTP) score
Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
ChronicLiver Disease Questionnaire (CLDQ)
Incidence of liver cancer
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

Full Information

First Posted
January 26, 2022
Last Updated
January 26, 2022
Sponsor
Beijing 302 Hospital
Collaborators
Chinese PLA General Hospital, Shanghai Changzheng Hospital, LanZhou University, Renmin Hospital of Wuhan University, Jin Yin-tan Hospital, Hainan Hospital of Chinese PLA General Hospital, VCANBIO Cell & Gene Engineering Corporation, Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05224960
Brief Title
Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-2)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing 302 Hospital
Collaborators
Chinese PLA General Hospital, Shanghai Changzheng Hospital, LanZhou University, Renmin Hospital of Wuhan University, Jin Yin-tan Hospital, Hainan Hospital of Chinese PLA General Hospital, VCANBIO Cell & Gene Engineering Corporation, Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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. 240 decompensated cirrhosis patients will be recruited in China.120 patients will receive i.v. transfusion 3 times of MSCs and the standard of care as the treated group. In addition, the 120 patients will receive placebo and standard of care as control group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Decompensated Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled, multicenter study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Arm Type
Experimental
Arm Description
UC-MSCs plus standard of care (SOC).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo plus SOC.
Intervention Type
Biological
Intervention Name(s)
UC-MSCs
Intervention Description
3 doses of UC-MSCs intravenously at week 0, week 4, week 8.
Intervention Type
Biological
Intervention Name(s)
Placebo(solution without UC-MSCs)
Intervention Description
3 doses of placebo intravenously at week 0, week 4, week 8.
Primary Outcome Measure Information:
Title
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 24th week
Description
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.
Time Frame
at 24th week
Secondary Outcome Measure Information:
Title
Change in MELD score from baseline to 96 weeks
Time Frame
up to 96 weeks
Title
Incidence of each complication associated with decompensated cirrhosis
Time Frame
up to 96 weeks
Title
liver transplant-free survival
Time Frame
up to 96 weeks
Title
Incidence of liver failure
Time Frame
up to 96 weeks
Title
plasma albumin (ALB)
Time Frame
up to 96 weeks
Title
plasma prealbumin (PALB)
Time Frame
up to 96 weeks
Title
total bilirubin (TBIL)
Time Frame
up to 96 weeks
Title
serum cholinesterase (CHE)
Time Frame
up to 96 weeks
Title
prothrombin activity (PA)
Time Frame
up to 96 weeks
Title
Child-Turcotte-Pugh (CTP) score
Description
Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
Time Frame
up to 96 weeks
Title
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Time Frame
up to 96 weeks
Title
ChronicLiver Disease Questionnaire (CLDQ)
Time Frame
up to 96 weeks
Title
Incidence of liver cancer
Time Frame
up to 96 weeks
Title
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Time Frame
up to 96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Shi, MD,PhD
Phone
86-10-66949623
Email
shilei302@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Fu-Sheng Wang, MD,PhD
Phone
86-10-66933332
Email
fswang302@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fu-Sheng Wang, MD, PhD
Organizational Affiliation
Beijing 302 Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
The First Hospital of Lanzhou University
City
Lanzhou
State/Province
Gansu
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xun Li
Email
lix@lzu.edu.cn
Facility Name
Hainan hospital of Chinese PLA General Hospital
City
Sanya
State/Province
Hainan
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ya-Li Zhao
Email
zhaoyl301@163.com
Facility Name
Jin Yin-tan hospital
City
Wuhan
State/Province
Hubei
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chaolin Huang
Email
88071718@qq.com
Facility Name
Renmin Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ying-an Jiang
Email
jiangya_cn@aliyun.com
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei-Fen Xie, MD, PhD
Email
weifenxie@medmail.com.cn
Facility Name
Beijing 302 Hospital
City
Beijing
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lei Shi, MD, PhD
Phone
86-10-66949623
Email
shilei302@126.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.

Learn more about this trial

Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-2)

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