Clinical trial NCT01741090: The Effectiveness and Safety for Mesenchymal Stem Cell for Alcoholic Liver Cirrhosis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alcoholic Liver Cirrhosis
Keywords: Autologous Mesenchymal stem cell
alcoholic liver cirrhosis
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2012-12-04
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: The improvement of Liver Histologic grade
timeFrame: 6 months later
Secondary outcomes:
measure: The evaluation of hepatic dendritic cells activity by immunohistochemistry
timeFrame: baseline and 6 months later
measure: Liver fibrosis quantitative analysis using Hydroxyproline contents in liver tissue
timeFrame: baseline and 6 months later
measure: Real-Time Polymerase Chain Reaction for relative mRNA expression of TGF-beta, collagen, procollagen, MMP2 or 9
timeFrame: baseline and 6 months later
measure: Hepatic venous pressure gradient(HVPG)
timeFrame: baseline and 6 months later
measure: Hepatic vein arrival time using microbubble contrast enhanced ultrasonography
timeFrame: baseline and 6 months later
measure: Liver stiffness measurement with transient elastography
timeFrame: baseline and 6 months later
measure: Child-Pugh score
timeFrame: baseline and 6 months later
measure: MELD score
timeFrame: baseline and 6 months later
Other outcomes:
Locations:
city: Wonju
country: Korea, Republic of
facility: Yonsei University Wonju College of Medicine Wonju Christian Hospital
state: Kangwon-do
Study officials:
affiliation: Yonsei University Wonju College of Medicine Department of Internal Medicine Devision of Gastroenterology and Hepatology
name: Soon Koo Baik, M.D
role: PRINCIPAL_INVESTIGATOR
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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.
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