Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-1)
Primary Purpose
Decompensated Cirrhosis
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Human Umbilical Cord-derived Mesenchymal Stem Cells
Sponsored by
About this trial
This is an interventional treatment trial for Decompensated Cirrhosis
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.
Sites / Locations
- Beijing 302 HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Human Umbilical Cord-derived Mesenchymal Stem Cells
Arm Description
Standard of care (SOC) plus a dose-escalation with 4 cohorts with 3-6 subjects/cohort who receive doses of 5, 10,15 and 20 ×10E7 cells. Proceed from lower dose to next higher dose if no safety concerns for each cohort.
Outcomes
Primary Outcome Measures
Incidence of Adverse Events Incidence of Adverse Events
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.
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).
Secondary Outcome Measures
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 3 days, 7days, 14 days, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months
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 time (PT)
Prothrombin time (PT) is a blood test that measures the time it takes for plasma to clot, to check for bleeding problems, or to check whether medicine to prevent blood clots is working.
Child-Turcotte-Pugh (CTP) score
Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
Maximum is 15, minimum is 5. Higher scores mean a worse outcome.
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Quality of life assessment. Maximum is 5, minimum is 1. Lower scores mean a better outcome.
Incidence of liver cancer
ChronicLiver Disease Questionnaire (CLDQ)
Quality of life assessment. The Chronic Liver Disease Questionnaire (CLDQ) was developed as an evaluative instrument to measure longitudinal change in health status within individuals with chronic liver disease. In addition to measuring both physical and mental health, the instrument was designed to be a disease-specific tool for assessing areas of function important to patients with chronic liver disease. Maximum is 7, minimum is 1. Higher scores mean a better outcome.
Full Information
NCT ID
NCT05227846
First Posted
January 26, 2022
Last Updated
April 25, 2023
Sponsor
Beijing 302 Hospital
Collaborators
VCANBIO Cell & Gene Engineering Corporation, Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05227846
Brief Title
Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-1)
Official Title
A Phase 1 Dose Escalation Study of Human Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Decompensated Cirrhosis (MSC-DLC-1)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing 302 Hospital
Collaborators
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
This is a Phase 1, open label, dose escalation clinical trial of human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated cirrhosis. The purpose of this study is to assess the safety of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.
Detailed Description
The primary objective of this study is to assess the safety of intravenous infusion of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.
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 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Human Umbilical Cord-derived Mesenchymal Stem Cells
Arm Type
Experimental
Arm Description
Standard of care (SOC) plus a dose-escalation with 4 cohorts with 3-6 subjects/cohort who receive doses of 5, 10,15 and 20 ×10E7 cells. Proceed from lower dose to next higher dose if no safety concerns for each cohort.
Intervention Type
Biological
Intervention Name(s)
Human Umbilical Cord-derived Mesenchymal Stem Cells
Intervention Description
Human Umbilical Cord-derived Mesenchymal Stem Cells will be administered intravenously.
Primary Outcome Measure Information:
Title
Incidence of Adverse Events Incidence of Adverse Events
Time Frame
from baseline to 28th day
Title
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
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.
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).
Time Frame
at 28th day
Secondary Outcome Measure Information:
Title
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 3 days, 7days, 14 days, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months
Time Frame
3 days, 14 days, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months
Title
Incidence of each complication associated with decompensated cirrhosis
Time Frame
up to 24 months
Title
liver transplant-free survival
Time Frame
up to 24 months
Title
Incidence of liver failure
Time Frame
up to 24 months
Title
plasma albumin (ALB)
Time Frame
up to 24 months
Title
plasma prealbumin (PALB)
Time Frame
up to 24 months
Title
total bilirubin (TBIL)
Time Frame
up to 24 months
Title
serum cholinesterase (CHE)
Time Frame
up to 24 months
Title
prothrombin time (PT)
Description
Prothrombin time (PT) is a blood test that measures the time it takes for plasma to clot, to check for bleeding problems, or to check whether medicine to prevent blood clots is working.
Time Frame
up to 24 months
Title
Child-Turcotte-Pugh (CTP) score
Description
Child-Turcotte-Pugh (CTP) score is a scoring system that evaluates the liver function.
Maximum is 15, minimum is 5. Higher scores mean a worse outcome.
Time Frame
up to 24 months
Title
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)
Description
Quality of life assessment. Maximum is 5, minimum is 1. Lower scores mean a better outcome.
Time Frame
up to 24 months
Title
Incidence of liver cancer
Time Frame
up to 24 months
Title
ChronicLiver Disease Questionnaire (CLDQ)
Description
Quality of life assessment. The Chronic Liver Disease Questionnaire (CLDQ) was developed as an evaluative instrument to measure longitudinal change in health status within individuals with chronic liver disease. In addition to measuring both physical and mental health, the instrument was designed to be a disease-specific tool for assessing areas of function important to patients with chronic liver disease. Maximum is 7, minimum is 1. Higher scores mean a better outcome.
Time Frame
up to 24 months
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
Beijing 302 Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
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-1)
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