Back to resultsClinical Study of hUC-MSCs Treating Decompensated Liver Cirrhosis With HBV (CS-hUC-MSCs)
Primary Purpose
HBV
Status
Completed
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
hUCMSCs
Sponsored by
About this trial
This is an interventional treatment trial for HBV
Eligibility Criteria
Inclusion Criteria:
- Aged between 18 and 65 (including 18 and 65), regardless of gender;
- Decompensated stage of viral hepatitis B cirrhosis;
- The effect of conventional medical treatment is not good, and the condition is repeated;
- ALB < 35g/L, TBIL < 170μmol/L, INR > 30%, Child-pugh score ≥7; MELD score ≤15;
- Hgb > 70g/L, PLT > 3×109/L;
- Unconditional acceptance for liver transplantation; 7）Participate in the clinical study voluntarily, cooperate with doctors to carry out the study, and sign informed consent.
Exclusion Criteria:
- With spontaneous peritonitis or other serious infection;
- Patients with hepatorenal syndrome;
- Severe hepatic encephalopathy, massive hemorrhage of digestive tract or varicose 4. vein in recent 1 month;
- Portal vein thrombosis; Complicated with serious diseases of heart, lung, kidney,
- blood and endocrine system;
- HIV positive;
- Positive autoantibodies related to autoimmune liver disease;
- Presence of liver or any type of malignant tumor;
- Pregnant women, breast-feeding women or those with recent birth plans;
- Those who have a history of alcohol and drug abuse and failed to get rid of it effectively;
- Participated in other clinical trials within 3 months prior to enrollment;
- Participated in clinical research on stem cells;
- Unwillingness to sign informed consent;
- Other conditions that the investigator considers inappropriate for patients to participate in this study.
Sites / Locations
- Zhongnan Hospital of Wuhan University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Low-dose group
medium-dose group
High-dose group
Arm Description
100mL human umbilical cord mesenchymal stem cell preparation, containing 2.5×10^7 cells.
100mL human umbilical cord mesenchymal stem cell preparation, containing 5.0×10^7 cells.
100mL human umbilical cord mesenchymal stem cell preparation, containing 1.0×10^8 cells.
Outcomes
Primary Outcome Measures
Serum albumin in g/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
alanine aminotransferase in U/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
aspartate aminotransferase in U/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
cholinesterase in U/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Total bilirubin in μmol/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Direct bilirubin in μmol/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Serum cholesterol in mmol/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Prothrombin activity in percentage
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Antithrombin in mg/L
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Secondary Outcome Measures
survival rate
survival rate after 2 years since the first therapy
Child-Pugh grade
Child-Pugh grade is defined according to hepatic encephalopathy, ascites，serum albumin, total bilirubin, prothrombin time. Score 5-6 is grade A. Score 7-9 is grade B. Score 10-15 is grade C.
We compare the Child-Pugh grade in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Rate of weight change
We compare the weight in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Ascites
We test the ascites via ultrasound, CT and MRI. We classify the ascite level into none, low and high.
We compare the Child-Pugh grade in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
clinical symptoms
Including lower limb edema, hematemesis, jaundice, fatigue, poor appetite. We compare these symptoms in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Th1 cells in percentage
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Th2 cells in percentage
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Natural killer T cells in percentage
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-1β cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-4 cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-6 cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-8 cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-12 cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-15 cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Interleukin-17A cells in pg/mL
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Medical images
Ultrasound in first day, 4th, 8th, 12th and 24th; enhanced CT scanning and/or MRI-Primovist scanning in first day, 12th week and 24th week.
The Medical outcomes study 36-item Short Form Health Survay scale (SF-36 scale)
SF-36 scale is a measurement for patients' living quality. The scores contain 8 parts, including physical functioning, role-physica, bodily pain, general health, vitality, social functioning, role-emotional and mental health. Conversion score=(actual score-minimum score in this part)/(maximum score in this part-minimum score in this part)*100. Score of each part range from 0 to 100. The higher score means more healthy. We proceed SF-36 test in 12th week and 24th week
MELD score
MELD=3.78*Ln(total bilirubin mg/dL)+11.2*Ln(INR)+9.57*Ln(serum creatine mg/dL)+6.43 (for HBV patient) We compare MELD score in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05442437
Brief Title
Clinical Study of hUC-MSCs Treating Decompensated Liver Cirrhosis With HBV
Acronym
CS-hUC-MSCs
Official Title
Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells for Treating Decompensated Liver Cirrhosis Associated With HBV
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
September 8, 2019 (Actual)
Primary Completion Date
July 1, 2022 (Actual)
Study Completion Date
December 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zhongnan Hospital
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
The purpose of this study was to observe the safety ,tolerability ,Efficacy dose of human umbilical cord mesenchymal stem cells in patients of decompensated liver cirrhosis with HBV.
Detailed Description
Investigators plan to recruit 24 voluntary patients of decompensate liver cirrhosis with HBV, dividing them into 3 group：1) low-dose group: 100mL with 2.5×10^7 cells；2) medium-dose group: 100mL with 5.0×10^7 cells；3) high-dose group: 100mL with 1.0×10^8 cells. Each group contains 8 patients. Investigators treat the participants with human umbilical cord mesenchymal stem cells via venous transfusion. First investigators arrange a whole test for participants, such as vital sign examination, laboratory test, ECG, CT, MRI, ultrasound etc. Investigators screen these patients with a complete eligibility criteria. Then investigators proceed the therapy in the 1st, 8th and 15th day. There are 8 times of follow-up visit for these patients, 4 times of those are proceeded during the hospitalization, while other 4 times happens after the discharge. The follow-up visit includes vital sign examination, laboratory test, ECG, CT, MRI, ultrasound, Child-Pugh grade, MELD grade, SF-36 test. These follow-up visit last 24 weeks since the first treatment. After that, investigators also arrange a survival visit through phone or clinic each 6 months, lasting another 1.5 years. The main object of this research is investigating the survival rate, promotion of the liver function, improvement of health, safety of hUC-MSCs, tolerability of patients, for exploring a new way for the therapy of decompensated liver cirrhosis with HBV.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HBV
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Model Description
We allocate 24 participants into 3 group, low-dose, medium-dose and high-dose group. It is going to proceeded sequential from low-dose group to high-dose group. Next group is allowed to be started only the last group has been finished.
Low-dose group: 100mL human umbilical cord mesenchymal stem cell preparation, containing 2.5×10^7 cells;
medium-dose group: 100mL human umbilical cord mesenchymal stem cell preparation, containing 5.0×10^7 cells;
High-dose group: 100mL human umbilical cord mesenchymal stem cell preparation, containing 1.0×10^8 cells
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low-dose group
Arm Type
Experimental
Arm Description
100mL human umbilical cord mesenchymal stem cell preparation, containing 2.5×10^7 cells.
Arm Title
medium-dose group
Arm Type
Experimental
Arm Description
100mL human umbilical cord mesenchymal stem cell preparation, containing 5.0×10^7 cells.
Arm Title
High-dose group
Arm Type
Experimental
Arm Description
100mL human umbilical cord mesenchymal stem cell preparation, containing 1.0×10^8 cells.
Intervention Type
Biological
Intervention Name(s)
hUCMSCs
Intervention Description
Human umbilical cord mesenchymal stem cell preparation, 100ml/ bag, containing 2.5×107 cells, 5.0×107 cells, 1.0 x 108 cells
Primary Outcome Measure Information:
Title
Serum albumin in g/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
alanine aminotransferase in U/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
aspartate aminotransferase in U/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
cholinesterase in U/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Total bilirubin in μmol/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Direct bilirubin in μmol/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Serum cholesterol in mmol/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Prothrombin activity in percentage
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Antithrombin in mg/L
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
survival rate
Description
survival rate after 2 years since the first therapy
Time Frame
2 years
Title
Child-Pugh grade
Description
Child-Pugh grade is defined according to hepatic encephalopathy, ascites，serum albumin, total bilirubin, prothrombin time. Score 5-6 is grade A. Score 7-9 is grade B. Score 10-15 is grade C.
We compare the Child-Pugh grade in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Time Frame
24 weeks
Title
Rate of weight change
Description
We compare the weight in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Time Frame
24 weeks
Title
Ascites
Description
We test the ascites via ultrasound, CT and MRI. We classify the ascite level into none, low and high.
We compare the Child-Pugh grade in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Time Frame
24 weeks
Title
clinical symptoms
Description
Including lower limb edema, hematemesis, jaundice, fatigue, poor appetite. We compare these symptoms in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Th1 cells in percentage
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Th2 cells in percentage
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Natural killer T cells in percentage
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-1β cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-4 cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-6 cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-8 cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-12 cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-15 cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Interleukin-17A cells in pg/mL
Description
We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Medical images
Description
Ultrasound in first day, 4th, 8th, 12th and 24th; enhanced CT scanning and/or MRI-Primovist scanning in first day, 12th week and 24th week.
Time Frame
24 weeks
Title
The Medical outcomes study 36-item Short Form Health Survay scale (SF-36 scale)
Description
SF-36 scale is a measurement for patients' living quality. The scores contain 8 parts, including physical functioning, role-physica, bodily pain, general health, vitality, social functioning, role-emotional and mental health. Conversion score=(actual score-minimum score in this part)/(maximum score in this part-minimum score in this part)*100. Score of each part range from 0 to 100. The higher score means more healthy. We proceed SF-36 test in 12th week and 24th week
Time Frame
24 weeks
Title
MELD score
Description
MELD=3.78*Ln(total bilirubin mg/dL)+11.2*Ln(INR)+9.57*Ln(serum creatine mg/dL)+6.43 (for HBV patient) We compare MELD score in first day, 4th, 8th, 12th and 24th week, to describe its tendency.
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Adverse events
Description
Including infusion reaction, anaphylaxis, hemolysis, acute liver failure, acute kidney failure. We observe whether participants shows these adverse event during the first whole 2 weeks and 4th, 8th, 12th and 24th weeks
Time Frame
24 weeks
Title
Vital signs
Description
body temperature, pulse, respiration, blood pressure. We measure the vital signs in first day, 1st , 2nd, 3rd, 4th, 8th, 12th and 24th week.
Time Frame
24 weeks
Title
Physical examination
Description
Including jaundice in skin or sclera, liver palms, spider angioma, abdominal tenderness, borborygms, shifting dullness. We proceed the physical examination in first day, 1st , 2nd, 3rd, 4th, 8th, 12th and 24th week.
Time Frame
24 weeks
Title
Leukocyte in 10^9/L
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Hemoglobin in g/L
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Thrombocyte in 10^9/L
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Serum creatine in
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Serum creatine in μmol/L
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Serum urea nitrogen in mmol/L
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Alpha-fetoprotein in ng/mL
Description
We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.
Time Frame
24 weeks
Title
Electrocardiogram of 12 leads
Description
Including lead I, II, III, AVL, AVF, AVR, V1 to V6. We record the diagnosis of the ECG, not a specific parameter. We test it in first day, 4th, 8th, 12th and 24th week.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged between 18 and 65 (including 18 and 65), regardless of gender;
Decompensated stage of viral hepatitis B cirrhosis;
The effect of conventional medical treatment is not good, and the condition is repeated;
ALB < 35g/L, TBIL < 170μmol/L, INR > 30%, Child-pugh score ≥7; MELD score ≤15;
Hgb > 70g/L, PLT > 3×109/L;
Unconditional acceptance for liver transplantation; 7）Participate in the clinical study voluntarily, cooperate with doctors to carry out the study, and sign informed consent.
Exclusion Criteria:
With spontaneous peritonitis or other serious infection;
Patients with hepatorenal syndrome;
Severe hepatic encephalopathy, massive hemorrhage of digestive tract or varicose 4. vein in recent 1 month;
Portal vein thrombosis; Complicated with serious diseases of heart, lung, kidney,
blood and endocrine system;
HIV positive;
Positive autoantibodies related to autoimmune liver disease;
Presence of liver or any type of malignant tumor;
Pregnant women, breast-feeding women or those with recent birth plans;
Those who have a history of alcohol and drug abuse and failed to get rid of it effectively;
Participated in other clinical trials within 3 months prior to enrollment;
Participated in clinical research on stem cells;
Unwillingness to sign informed consent;
Other conditions that the investigator considers inappropriate for patients to participate in this study.
Facility Information:
Facility Name
Zhongnan Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
12. IPD Sharing Statement
Learn more about this trial
Clinical Study of hUC-MSCs Treating Decompensated Liver Cirrhosis With HBV
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