Clinical trial NCT05442437: Clinical Study of hUC-MSCs Treating Decompensated Liver Cirrhosis With HBV
Official title: Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells for Treating Decompensated Liver Cirrhosis Associated With HBV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: HBV
Lead sponsor: Zhongnan Hospital
Sponsor class: OTHER
First posted: 2022-07-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.

1. Low-dose group: 100mL human umbilical cord mesenchymal stem cell preparation, containing 2.5×10\^7 cells;
2. medium-dose group: 100mL human umbilical cord mesenchymal stem cell preparation, containing 5.0×10\^7 cells;
3. High-dose group: 100mL human umbilical cord mesenchymal stem cell preparation, containing 1.0×10\^8 cells
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Serum albumin in g/L
timeFrame: 24 weeks
measure: alanine aminotransferase in U/L
timeFrame: 24 weeks
measure: aspartate aminotransferase in U/L
timeFrame: 24 weeks
measure: cholinesterase in U/L
timeFrame: 24 weeks
measure: Total bilirubin in μmol/L
timeFrame: 24 weeks
measure: Direct bilirubin in μmol/L
timeFrame: 24 weeks
measure: Serum cholesterol in mmol/L
timeFrame: 24 weeks
measure: Prothrombin activity in percentage
timeFrame: 24 weeks
measure: Antithrombin in mg/L
timeFrame: 24 weeks
Secondary outcomes:
measure: survival rate
timeFrame: 2 years
measure: Child-Pugh grade
timeFrame: 24 weeks
measure: Rate of weight change
timeFrame: 24 weeks
measure: Ascites
timeFrame: 24 weeks
measure: clinical symptoms
timeFrame: 24 weeks
measure: Th1 cells in percentage
timeFrame: 24 weeks
measure: Th2 cells in percentage
timeFrame: 24 weeks
measure: Natural killer T cells in percentage
timeFrame: 24 weeks
measure: Interleukin-1β cells in pg/mL
timeFrame: 24 weeks
measure: Interleukin-4 cells in pg/mL
timeFrame: 24 weeks
measure: Interleukin-6 cells in pg/mL
timeFrame: 24 weeks
measure: Interleukin-8 cells in pg/mL
timeFrame: 24 weeks
measure: Interleukin-12 cells in pg/mL
timeFrame: 24 weeks
measure: Interleukin-15 cells in pg/mL
timeFrame: 24 weeks
measure: Interleukin-17A cells in pg/mL
timeFrame: 24 weeks
measure: Medical images
timeFrame: 24 weeks
measure: The Medical outcomes study 36-item Short Form Health Survay scale (SF-36 scale)
timeFrame: 24 weeks
measure: MELD score
timeFrame: 24 weeks
Other outcomes:
measure: Adverse events
timeFrame: 24 weeks
measure: Vital signs
timeFrame: 24 weeks
measure: Physical examination
timeFrame: 24 weeks
measure: Leukocyte in 10^9/L
timeFrame: 24 weeks
measure: Hemoglobin in g/L
timeFrame: 24 weeks
measure: Thrombocyte in 10^9/L
timeFrame: 24 weeks
measure: Serum creatine in
timeFrame: 24 weeks
measure: Serum creatine in μmol/L
timeFrame: 24 weeks
measure: Serum urea nitrogen in mmol/L
timeFrame: 24 weeks
measure: Alpha-fetoprotein in ng/mL
timeFrame: 24 weeks
measure: Electrocardiogram of 12 leads
timeFrame: 24 weeks
Locations:
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
Study officials:
References: