Clinical Study of hUC-MSCs Treating Decompensated Liver Cirrhosis With HBV (CS-hUC-MSCs)

Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells for Treating Decompensated Liver Cirrhosis Associated With HBV

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.

Study Overview

• Status: Completed
• Conditions: HBV
• Intervention / Treatment: Biological: hUCMSCs

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Zhongnan Hospital of Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose group; 100mL human umbilical cord mesenchymal stem cell preparation, containing 2.5×10^7 cells.	Biological: hUCMSCs; Human umbilical cord mesenchymal stem cell preparation, 100ml/ bag, containing 2.5×107 cells, 5.0×107 cells, 1.0 x 108 cells
Experimental: medium-dose group; 100mL human umbilical cord mesenchymal stem cell preparation, containing 5.0×10^7 cells.	Biological: hUCMSCs; Human umbilical cord mesenchymal stem cell preparation, 100ml/ bag, containing 2.5×107 cells, 5.0×107 cells, 1.0 x 108 cells
Experimental: High-dose group; 100mL human umbilical cord mesenchymal stem cell preparation, containing 1.0×10^8 cells.	Biological: hUCMSCs; Human umbilical cord mesenchymal stem cell preparation, 100ml/ bag, containing 2.5×107 cells, 5.0×107 cells, 1.0 x 108 cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum albumin in g/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
alanine aminotransferase in U/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
aspartate aminotransferase in U/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
cholinesterase in U/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Total bilirubin in μmol/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Direct bilirubin in μmol/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Serum cholesterol in mmol/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Prothrombin activity in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Antithrombin in mg/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival rate	survival rate after 2 years since the first therapy	2 years
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.	24 weeks
Rate of weight change	We compare the weight in first day, 4th, 8th, 12th and 24th week, to describe its tendency.	24 weeks
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.	24 weeks
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.	24 weeks
Th1 cells in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Th2 cells in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Natural killer T cells in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-1β cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-4 cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-6 cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-8 cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-12 cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-15 cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Interleukin-17A cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
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.	24 weeks
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	24 weeks
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.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	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	24 weeks
Vital signs	body temperature, pulse, respiration, blood pressure. We measure the vital signs in first day, 1st , 2nd, 3rd, 4th, 8th, 12th and 24th week.	24 weeks
Physical examination	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.	24 weeks
Leukocyte in 10^9/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Hemoglobin in g/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Thrombocyte in 10^9/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Serum creatine in	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Serum creatine in μmol/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Serum urea nitrogen in mmol/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Alpha-fetoprotein in ng/mL	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Electrocardiogram of 12 leads	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.	24 weeks

Collaborators and Investigators

• Sponsor: Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2019
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No