REVIVE(Randomized Exploratory Clinical Trial to Evaluate the Safety and Effectiveness of Stem Cell Product in Alcoholic Liver Cirrhosis Patient)

Study Overview
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Brief Summary
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If the participant voluntarily agrees to participate in the clinical trial before registration, the investigator conducts a screening test to evaluate the participant's suitability. A participant that satisfies all selection and exclusion criteria is assigned randomly to a test group (1-time or 2-time injection group) or control group (no-cell therapy group). Participants assigned to the 1-time injection group conduct cell therapy within 1 month after bone marrow aspiration. Before implementing cell therapy, implement hepatic artery catheterization which inserts a catheter into the hepatic artery through the right aorta femoralis and inject 5X107 autologous bone marrow-derived mesenchymal stem cells. Participants assigned to the 2-time injection group store 1-time injection amount of mesenchymal stem cells while being cultivated after sampled from the bone marrow, and will re-inject autologous mesenchymal stem cells within 1 month after first injection. Participants will make a total of 8 hospital visits on a 4-week interval after registration, and effectiveness and safety will be evaluated based on a fixed procedure on every visit.

Official Title
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Randomized Exploratory Clinical Trial to Evaluate the Safety and Effectiveness of Stem Cell Product in Alcoholic Liver Cirrhosis Patient.

Conditions
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Alcoholic Liver Cirrhosis

Intervention / Treatment
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* Biological: Livercellgram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or clinically diagnosed as alcoholic liver cirrhosis Classified as Child-Pugh grade B or C Age of 20   70 years Capable of conducting hepatic artery catheterization which inserts a catheter up to the hepatic artery In the case of fertile women, confirmed as negative in pregnancy test when screening, and agreed to avoid pregnancy during the trial period Women capable of pregnancy must satisfy the following conditions; Has been through menopause for at least 1 year, has no possibility of pregnancy via surgery/procedure, or effectively used acceptable contraceptive methods (Intrauterine device-loop, mirena, diaphragm or condom/femidom, oral contraceptive pills, non-oral contraceptives) Patient who can agree to participate in the clinical trial by oneself or by one's legal representative Able to conduct the clinical trial according to the protocol Exclusion Criteria: Diagnosed with malignant hematologic disease (acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma) and not cured from it Patient with severe aplastic anemia Has a medical record of solid cancer(within 5 years prior to screening), or diagnosed with solid cancer and currently receiving cancer treatment Incapable of conducting hepatic artery Patient who consumed alcohol and took hepatotoxic drugs within 6 months prior to registration Has continuously taken a large amount of steroids or antibiotics for 1 month prior to registration Judged by a researcher to have had major orthopedic surgery, organ biopsy, or similar external injury within 3 months prior to registration Evidence of active autoimmune liver disease Patient with extrahepatic biliary stricture Patient who conducted transjugular intrahepatic portosystemic shunt Has active thrombosis of the portal or hepatic veins Patient with sepsis Patient who suffers heart, renal, respiratory failure Patient who is positive in pathogenic test (HIV, Syphilis,HBV,HCV) Pregnant or lactating woman Patient who cannot adapt to the protocol and follow-up observation Patient who has experienced drug abuse for the past 1 year Participated in the other clinical trials within 30 days before registration Patient with any disease or condition which the investigator feel would interfere with trial or the safety of the subject

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Best Supportive care | |
| Experimental: 1-time injection group: Livercellgram<br>Within 1 month after extracting bone marrow, directly inject 5X107 autologous bone marrow-derived mesenchymal stem cells within liver through the hepatic artery. | Biological: Livercellgram<br>* Livercellgram Dosage form and appearance: White cell suspension is filled in a clear plastic syringe, and fixed with an occlude on the prefilled syringe tip ② Component: Autologous bone marrow-derived mesenchymal stem cell ③ Amount: 5X107 cells, 1-time or 2-time injection ④ Storage Method: Stored in airtight container at 20 25℃ Injection Method: Directly inject into liver through hepatic artery<br>* Other names: Autologous bone marrow-derived mesenchymal stem cell;|
| Experimental: 2-time injection group: Livercellgram<br>Within 1 month after extracting bone marrow, directly inject 5X107 autologous bone marrow-derived mesenchymal stem cells within liver through the hepatic artery. Within 1 month after cell injection, re-inject autologous bone marrow-derived mesenchymal stem cells. | Biological: Livercellgram<br>* Livercellgram Dosage form and appearance: White cell suspension is filled in a clear plastic syringe, and fixed with an occlude on the prefilled syringe tip ② Component: Autologous bone marrow-derived mesenchymal stem cell ③ Amount: 5X107 cells, 1-time or 2-time injection ④ Storage Method: Stored in airtight container at 20 25℃ Injection Method: Directly inject into liver through hepatic artery<br>* Other names: Autologous bone marrow-derived mesenchymal stem cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological evaluation (Fibrosis Grade - Laennec Scoring System) |  | 6 month after cell therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological evaluation score (Ratio of 1-time injection group to 2-time injection group comparison) |  | 6month | 
| MELD Score |  | 6month | 
| Child-Pugh grade |  | 6month | 
| Liver Function Test (ALT, AST, ALP, Albumin, billirubin, r-GT) |  | 6month | 
| Visual Inspection (Liver volume, Fibroscan) |  | 6month |