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

NCT01741090 | Unknown Phase 2 DMC

• 1 other identifier: CR109021
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alcoholic Liver Cirrhosis

Keywords

Autologous Mesenchymal stem cell; alcoholic liver cirrhosis

Outcome Measures

Primary Outcomes (1)

• The improvement of Liver Histologic grade

  according to Metavir and Laennec fibrosis scoring system

  6 months later

Secondary Outcomes (8)

• The evaluation of hepatic dendritic cells activity by immunohistochemistry

  baseline and 6 months later

• Liver fibrosis quantitative analysis using Hydroxyproline contents in liver tissue

  baseline and 6 months later

• Real-Time Polymerase Chain Reaction for relative mRNA expression of TGF-beta, collagen, procollagen, MMP2 or 9

  baseline and 6 months later

• Hepatic venous pressure gradient(HVPG)

  baseline and 6 months later

• Hepatic vein arrival time using microbubble contrast enhanced ultrasonography

  baseline and 6 months later

Study Arms (1)

MSC injection

EXPERIMENTAL

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

Interventions

mesenchymal stem cell injection BIOLOGICAL

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.

MSC injection

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Alcoholic liver cirrhosis(child Pugh class B or C, ≥ 7 scores),confirmed by clinically or biopsy.
• Stop drinking over past 6months.

You may not qualify if:

• Hepatocellular carcinoma
• Pregnancy or breast feeding
• Infective disease(HIV, HBV, HCV..)
• Other incurable malignancy

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Wonju College of Medicine Wonju Christian Hospital

Wŏnju, Gangwon-do, 220-701, South Korea

RECRUITING

Related Publications (9)

• 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.

  PMID: 6743531 BACKGROUND

• Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995 Dec;19(12):1409-17. doi: 10.1097/00000478-199512000-00007.

  PMID: 7503362 BACKGROUND

• 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. doi: 10.1016/j.bbrc.2005.03.086.

  PMID: 15823564 BACKGROUND

• 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. doi: 10.1002/hep.20469.

  PMID: 15562440 BACKGROUND

• 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. doi: 10.3748/wjg.v11.i47.7461.

  PMID: 16437717 BACKGROUND

• Kallis YN, Alison MR, Forbes SJ. Bone marrow stem cells and liver disease. Gut. 2007 May;56(5):716-24. doi: 10.1136/gut.2006.098442. Epub 2006 Dec 4. No abstract available.

  PMID: 17145739 BACKGROUND

• 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. doi: 10.1631/jzus.2006.B0641.

  PMID: 16845718 BACKGROUND

• 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.

  PMID: 21354227 BACKGROUND

• Jang YO, Kim YJ, Baik SK, Kim MY, Eom YW, Cho MY, Park HJ, Park SY, Kim BR, Kim JW, Soo Kim H, Kwon SO, Choi EH, Kim YM. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver Int. 2014 Jan;34(1):33-41. doi: 10.1111/liv.12218. Epub 2013 Jun 19.

  PMID: 23782511 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Alcoholic

Condition Hierarchy (Ancestors)

Liver Cirrhosis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Soon Koo Baik, M.D

  Yonsei University Wonju College of Medicine Department of Internal Medicine Devision of Gastroenterology and Hepatology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soon Koo Baik, M.D., PhD

CONTACT

82-33-741-1229; baiksk@medimail.co.kr

Moon Young Kim, M.D., PhD

CONTACT

82-33-741-1225; drkimmy@yonsei.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: December 4, 2012
• Study Start: September 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 10, 2012

Record last verified: 2012-12

Locations

KR (1)