The Effectiveness and Safety for Mesenchymal Stem Cell for Alcoholic Liver Cirrhosis
Background & Aim: Bone marrow derived mesenchymal stem cells (BM-MSCs) have capacity to differentiate into hepatocytes and anti-fibrotic effect in the experimental model. No study was done in humans with alcoholic liver cirrhosis. The researchers investigated the anti-fibrotic effect of BM-MSCs in alcoholic cirrhosis as Phase II clinical study.
Methods: Eleven alcoholic cirrhosis patients (M:F = 10:1) with Child-Pugh's class B and maintenance of alcohol abstinence at least 2 months were enrolled. At baseline, all patients received liver biopsy, hepatic venous pressure gradient (HVPG) measurement and serologic tests. BM-MSCs were isolated from each patient's BM and amplified for one month and injected two times at 4, 8week through Rt. hepatic artery. 5x106cells/mL of BM-MSCs were injected in each session. Follow up biopsy, HVPG and relative expression of tissue transforming growth factor-1 (TGF-β1), α smooth muscle actin (α-SMA) and collagen-1 by real time RT PCR were measured after 12weeks from 2nd BM-MSC injection. The primary outcome was improvement in patients' histology Aim :
The researchers aimed to evaluate safety and effectiveness of new therapy with bone marrow derived autologous mesenchymal stem cell for hepatic failure caused by alcoholic liver cirrhosis.
Alcoholic Liver Cirrhosis
Biological: mesenchymal stem cell injection
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Evaluation of Effectiveness and Safety for New Therapy With Bone Marrow Derived Autologous Mesenchymal Stem Cell for Hepatic Failure Caused by Alcoholic Liver Cirrhosis|
- The improvement of Liver Histologic grade [ Time Frame: 6 months later ] [ Designated as safety issue: Yes ]according to Metavir and Laennec fibrosis scoring system
- The evaluation of hepatic dendritic cells activity by immunohistochemistry [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]
- Liver fibrosis quantitative analysis using Hydroxyproline contents in liver tissue [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]Hydroxyproline is a essential component of collange fiber
- Real-Time Polymerase Chain Reaction for relative mRNA expression of TGF-beta, collagen, procollagen, MMP2 or 9 [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]
- Hepatic venous pressure gradient(HVPG) [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]HVPG is a gold standard to measure the portal hypertension.
- Hepatic vein arrival time using microbubble contrast enhanced ultrasonography [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]Hepatic vein arrival time is related with portal hypertension and intrahepatic inflammation, neoangiogenesis and shunts formation secondary to hepatic fibrosis.
- Liver stiffness measurement with transient elastography [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]Recently, hepatic fibrosis can be estimated non-invasively using transient elastography (Fibroscan, commercial name) and it can be additive data in estimation of therapeutic response.
- Child-Pugh score [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]
- MELD score [ Time Frame: baseline and 6 months later ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: MSC injection
This study is designed as single interventional arm without comparative arm. MSC injection means hepatic artery catheterizations and mesenchymal stem cell injection through catheter.
Biological: mesenchymal stem cell injection
Hepatic artery catheterization and mesenchymal stem cell injection will be used in alcoholic liver cirrhosis. And before and 1 month after injection, change of liver cirrhosis and portal hypertension will be evaluated.
Autologous BM-MSCs therapy in alcoholic cirrhosis induces improvement of hepatic fibrosis in histological and quantitative measurements.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01741090
|Contact: Soon Koo Baik, M.D., PhDfirstname.lastname@example.org|
|Contact: Moon Young Kim, M.D., PhDemail@example.com|
|Korea, Republic of|
|Yonsei University Wonju College of Medicine Wonju Christian Hospital||Recruiting|
|Wonju, Kangwon-do, Korea, Republic of, 220-701|
|Contact: Soon Koo Baik, M.D 82-33-741-1229 firstname.lastname@example.org|
|Contact: Moon Young Kim, M.D 82-33-741-1225 email@example.com|
|Principal Investigator: Soon Koo Baik, M.D|
|Sub-Investigator: Moon Young Kim, M.D|
|Principal Investigator:||Soon Koo Baik, M.D||Yonsei University Wonju College of Medicine Department of Internal Medicine Devision of Gastroenterology and Hepatology|