The Effectiveness and Safety for Mesenchymal Stem Cell for Alcoholic Liver Cirrhosis

Alcoholic Liver Cirrhosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01741090
• Other study ID #: CR109021
• Status: Recruiting
• Phase: Phase 2
• First received: November 10, 2011
• Last updated: December 7, 2012
• Start date: September 2009
• Est. completion date: August 2013

Study information

• Verified date: December 2012
• Source: Yonsei University
• Contact: Soon Koo Baik, M.D., PhD
• Phone: 82-33-741-1229
• Email: baiksk[@]medimail.co.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationKorea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Autologous BM-MSCs therapy in alcoholic cirrhosis induces improvement of hepatic fibrosis in histological and quantitative measurements.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: August 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Alcoholic liver cirrhosis(child Pugh class B or C, = 7 scores),confirmed by clinically or biopsy.

2. Stop drinking over past 6months.

3. Patients agree with informed consent Patients must satisfy all inclusion criteria.

Exclusion Criteria:

1. Patients who did not satisfy inclusion criteria

2. Hepatocellular carcinoma

3. Pregnancy or breast feeding

4. Infective disease(HIV, HBV, HCV..)

5. Other incurable malignancy

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcoholic Liver Cirrhosis
• Liver Cirrhosis
• Liver Cirrhosis, Alcoholic

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University Wonju College of Medicine Wonju Christian Hospital	Wonju	Kangwon-do

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (8)

Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995 Dec;19(12):1409-17. — View Citation

Hong SH, Gang EJ, Jeong JA, Ahn C, Hwang SH, Yang IH, Park HK, Han H, Kim H. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem Biophys Res Commun. 2005 May 20;330(4):1153-61. — View Citation

Kallis YN, Alison MR, Forbes SJ. Bone marrow stem cells and liver disease. Gut. 2007 May;56(5):716-24. Epub 2006 Dec 4. Review. — View Citation

Kang XQ, Zang WJ, Bao LJ, Li DL, Song TS, Xu XL, Yu XJ. Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes. World J Gastroenterol. 2005 Dec 21;11(47):7461-5. — View Citation

Kim MY, Cho MY, Baik SK, Park HJ, Jeon HK, Im CK, Won CS, Kim JW, Kim HS, Kwon SO, Eom MS, Cha SH, Kim YJ, Chang SJ, Lee SS. Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension. J Hepatol. 2011 Nov;55(5):1004-9. doi: 10.1016/j.jhep.2011.02.012. Epub 2011 Feb 24. — View Citation

Kountouras J, Billing BH, Scheuer PJ. Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol. 1984 Jun;65(3):305-11. — View Citation

Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 2004 Dec;40(6):1275-84. — View Citation

Wang JA, Luo RH, Zhang X, Xie XJ, Hu XY, He AN, Chen J, Li JH. Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction. J Zhejiang Univ Sci B. 2006 Aug;7(8):641-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The improvement of Liver Histologic grade	according to Metavir and Laennec fibrosis scoring system	6 months later	Yes
Secondary	The evaluation of hepatic dendritic cells activity by immunohistochemistry		baseline and 6 months later	Yes
Secondary	Liver fibrosis quantitative analysis using Hydroxyproline contents in liver tissue	Hydroxyproline is a essential component of collange fiber	baseline and 6 months later	Yes
Secondary	Real-Time Polymerase Chain Reaction for relative mRNA expression of TGF-beta, collagen, procollagen, MMP2 or 9		baseline and 6 months later	Yes
Secondary	Hepatic venous pressure gradient(HVPG)	HVPG is a gold standard to measure the portal hypertension.	baseline and 6 months later	Yes
Secondary	Hepatic vein arrival time using microbubble contrast enhanced ultrasonography	Hepatic vein arrival time is related with portal hypertension and intrahepatic inflammation, neoangiogenesis and shunts formation secondary to hepatic fibrosis.	baseline and 6 months later	Yes
Secondary	Liver stiffness measurement with transient elastography	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.	baseline and 6 months later	Yes
Secondary	Child-Pugh score		baseline and 6 months later	Yes
Secondary	MELD score		baseline and 6 months later	Yes