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

Early Phase 1CompletedNCT05442437

Zhongnan Hospital24 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HBV

Interventions

hUCMSCsBIOLOGICAL

Human umbilical cord mesenchymal stem cell preparation, 100ml/ bag, containing 2.5×107 cells, 5.0×107 cells, 1.0 x 108 cells

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Outcomes

Primary Outcomes

Serum albumin in g/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

alanine aminotransferase in U/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

aspartate aminotransferase in U/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

cholinesterase in U/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

Total bilirubin in μmol/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

Direct bilirubin in μmol/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

Serum cholesterol in mmol/L

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

Prothrombin activity in percentage

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

Antithrombin in mg/L

Data from ClinicalTrials.gov

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Secondary Outcomes

survival rate

survival rate after 2 years since the first therapy

Time frame: 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.

Time frame: 24 weeks

Rate of weight change

We compare the weight in first day, 4th, 8th, 12th and 24th week, to describe its tendency.

Time frame: 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.

Time frame: 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.

Time frame: 24 weeks

Th1 cells in percentage

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 24 weeks

Th2 cells in percentage

We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 24 weeks