Safety and Efficacy Study of Umbilical Mesenchymal Stem Cells for Liver Cirrhosis

Study Overview
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Brief Summary
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Liver cirrhosis and subsequent liver failure are leading causes of morbidity and mortality worldwide. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis. Novel therapies are necessary to prevent or block the process of the disease. In this current prospective cohort, the investigators plan to organize four hospitals to determine the safety and efficacy of intravenous administration of umbilical mesenchymal stem cells in the treatment of patients with liver cirrhosis in next three years.

Official Title
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Clinical Trial of Umbilical Mesenchymal Stem Cells Transplantation for Liver Cirrhosis-Phase I/II

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Biological: mesenchymal stem cells
* Biological: Conventional therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent aged 30-60 years clinical diagnosis of compensated or decompensated liver child-Pugh B/C (7-12 points) expecting lifetime is over three years Exclusion Criteria: pregnant woman patient with severe vascular diseases patient with any organ failure patient with any tumors patient with HIV patient who has been transplanted patient treated with immunosuppressors patient for whom the follow-up is considered impossible patients with any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the subject

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Conventional therapy<br>only apply for conventional medical therapy without any cell therapy | Biological: Conventional therapy<br>* Conventional therapy without cell therapy<br>|
| Active Comparator: mesenchymal stem cells<br>combination of conventional therapy with umbilical mesenchymal stem cells intravenous injection, (4x107/40ml, once per three months, four times in one year) | Biological: mesenchymal stem cells<br>* Conventional therapy plus UC-MSC intravenous administration (4x107/40ml, once per three months, four times in one year)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival time |  | 3-year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum markers regarding liver and kidney function | liver functions：Albumin (ALB), Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), Prealbumin(PA), total bilirubin (TB), and direct bilirubin (DB) kidney function：Blood urea nitrogen (BUN), Urea (UA), and Crea (Cr) | 0, 3, 6, 9 and 12 months | 
| Serum markers regarding lipid and sugar profile | Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), very low density lipoprotein cholesterol (VLDL-C), and Non-HDL-C; blood sugar; | 0, 3, 6, 9 and 12 months | 
| Serum markers regarding cytokine profile | IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12(p40), IL-15, IL-17A, TNFα, TNFβ, IFN-γ, RANTES, TGFβ, lymphotactin, and C-reactive protein level (CRP) | 0, 3, 6, 9 and 12 months | 
| Serum levels of Hepatitis B and C | Serum levels of Hepatitis B and C | 0, 3, 6, 9 and 12 months | 
| tolerance and the adverse events | The classification for uncomfortable reaction is: 0, no discomfort; 1, slightly unwell, does not affect daily life; 2, moderate discomfort, affects daily life and work; 3, moderately unwell, significantly affects life, and bed rest; 4, severely unwell, life-threatening. A serious adverse event is defined as fatal, life threatening, permanently disabling, and tumors, particularly hepatocellular carcinoma. | 3-year follow up | 
| Changes of any clinical symptoms | abdominal distension, appetite, debilitation, and edema of lower limbs. | 3-year follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Umbilical Mesenchymal Stem Cells; Liver cirrhosis