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

HBV Clinical Trial

— CS-hUC-MSCs  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05442437
• Other study ID #: 03
• Status: Completed
• Phase: Early Phase 1
• Start date: September 8, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2021
• Source: Zhongnan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 31, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• HBV
• Liver Cirrhosis

Intervention

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

Locations

Country	Name	City	State
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Zhongnan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	Leukocyte in 10^9/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	Hemoglobin in g/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	Thrombocyte in 10^9/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	Serum creatine in	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	Serum creatine in µmol/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	Serum urea nitrogen in mmol/L	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	Alpha-fetoprotein in ng/mL	We test it in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Other	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
Primary	Serum albumin in g/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	alanine aminotransferase in U/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	aspartate aminotransferase in U/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	cholinesterase in U/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	Total bilirubin in µmol/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	Direct bilirubin in µmol/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	Serum cholesterol in mmol/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	Prothrombin activity in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Primary	Antithrombin in mg/L	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Secondary	survival rate	survival rate after 2 years since the first therapy	2 years
Secondary	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
Secondary	Rate of weight change	We compare the weight in first day, 4th, 8th, 12th and 24th week, to describe its tendency.	24 weeks
Secondary	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
Secondary	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
Secondary	Th1 cells in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Secondary	Th2 cells in percentage	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Secondary	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
Secondary	Interleukin-1ß cells in pg/mL	We compare this index in first day, 4th, 8th, 12th and 24th week, to describe their tendency.	24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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