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

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

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.

Study Overview

• Status: Completed
• Conditions: Alcoholic Liver Cirrhosis
• Intervention / Treatment: Biological: Livercellgram

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Pharmicell Co., Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or clinically diagnosed as alcoholic liver cirrhosis
2. Classified as Child-Pugh grade B or C
3. Age of 20 ~ 70 years
4. Capable of conducting hepatic artery catheterization which inserts a catheter up to the hepatic artery
5. In the case of fertile women, confirmed as negative in pregnancy test when screening, and agreed to avoid pregnancy during the trial period
6. 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)
7. Patient who can agree to participate in the clinical trial by oneself or by one's legal representative
8. Able to conduct the clinical trial according to the protocol

Exclusion Criteria:

1. Diagnosed with malignant hematologic disease (acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma) and not cured from it
2. Patient with severe aplastic anemia
3. Has a medical record of solid cancer(within 5 years prior to screening), or diagnosed with solid cancer and currently receiving cancer treatment
4. Incapable of conducting hepatic artery
5. Patient who consumed alcohol and took hepatotoxic drugs within 6 months prior to registration
6. Has continuously taken a large amount of steroids or antibiotics for 1 month prior to registration
7. Judged by a researcher to have had major orthopedic surgery, organ biopsy, or similar external injury within 3 months prior to registration
8. Evidence of active autoimmune liver disease
9. Patient with extrahepatic biliary stricture
10. Patient who conducted transjugular intrahepatic portosystemic shunt
11. Has active thrombosis of the portal or hepatic veins
12. Patient with sepsis
13. Patient who suffers heart, renal, respiratory failure
14. Patient who is positive in pathogenic test (HIV, Syphilis,HBV,HCV)
15. Pregnant or lactating woman
16. Patient who cannot adapt to the protocol and follow-up observation
17. Patient who has experienced drug abuse for the past 1 year
18. Participated in the other clinical trials within 30 days before registration
19. Patient with any disease or condition which the investigator feel would interfere with trial or the safety of the subject

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Best Supportive care
Experimental: 1-time injection group: Livercellgram; 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; 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; Other Names: Autologous bone marrow-derived mesenchymal stem cell
Experimental: 2-time injection group: Livercellgram; 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; 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; Other Names: Autologous bone marrow-derived mesenchymal stem cell

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Pharmicell Co., Ltd.
• Investigators: Principal Investigator: Soon Koo Baik, M.D.,Ph.D, Yonsei University, Wonju Christian Hospital; Principal Investigator: Si-Hyun Bae, M.D.,Ph.D, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 7, 2013
• First Submitted That Met QC Criteria: June 7, 2013
• First Posted (Estimate): June 11, 2013

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: March 16, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Alcohol-Related Disorders; Substance-Related Disorders; Liver Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Alcoholic
• Other Study ID Numbers: PMC-BD-CT-P-002