Mesenchymal Stem Cells Treat Liver Cirrhosis - Full Text View

Purpose

The purpose of this study is to investigate the efficacy of umbilical cord mesenchymal stem cells (MSCs) transfusion in the treatment of liver cirrhosis. Liver function will be monitored by serum analysis. The levels of serum alanine aminotransferase (ALT), total bilirubin (TB), prothrombin time (PT), prealbumin(PA) and albumin (ALB) will be examined at pre-transfusion, and 3 days to 2 years post-transfusion. Child-Pugh scores, Model for End-Stage Liver Disease scores and clinical symptoms will be assessed simultaneously.

Condition	Intervention	Phase
Liver Cirrhosis	Drug: Conserved Therapy Procedure: Hepatic artery infusion or Intravenous infusion	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Umbilical Cord Mesenchymal Stem Cell Transfusion in Patients With Severe Liver Cirrhosis

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Blood Transfusion and Donation Cirrhosis

U.S. FDA Resources

Further study details as provided by Chinese Academy of Sciences:

Primary Outcome Measures:

The level of serum alanine aminotransferase (ALT） [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The level of serum total bilirubin (TB) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The level of serum prothrombin time (PT) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The level of serum prealbumin(PA) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
The level of serum albumin (ALB) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

liver biopsy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The level of serum alanine aminotransferase (ALT） [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The level of serum total bilirubin (TB) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The level of serum prothrombin time (PT) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The level of serum albumin (ALB) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	October 2009
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Conserved Therapy Conserved Therapy	Drug: Conserved Therapy Conserved Therapy
Experimental: Interventional Therapy Patients with liver cirrhosis will be randomly divided into three groups. 1. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group.2. Umbilical cord MSCs will be infused to patients intravenously for another group. The control group will receive conserved therapy. The efficacy of different interventional therapies will be compared.	Procedure: Hepatic artery infusion or Intravenous infusion Patients with liver cirrhosis will be randomly divided into three groups. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group. The catheter will be inserted to proper hepatic artery. After the catheter placement confirmed by angiography, umbilical cord MSCs will be infused slowly in 20-30 minutes. Umbilical cord MSCs will be infused intravenously slowly for 30-60 minutes in the intravenous infusion group. The control group will receive conserved therapy.

Arms

Assigned Interventions

Active Comparator: Conserved Therapy

Conserved Therapy

Drug: Conserved Therapy

Conserved Therapy

Experimental: Interventional Therapy

Patients with liver cirrhosis will be randomly divided into three groups.

1. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group.2. Umbilical cord MSCs will be infused to patients intravenously for another group. The control group will receive conserved therapy. The efficacy of different interventional therapies will be compared.

Procedure: Hepatic artery infusion or Intravenous infusion

Patients with liver cirrhosis will be randomly divided into three groups. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group. The catheter will be inserted to proper hepatic artery. After the catheter placement confirmed by angiography, umbilical cord MSCs will be infused slowly in 20-30 minutes. Umbilical cord MSCs will be infused intravenously slowly for 30-60 minutes in the intravenous infusion group. The control group will receive conserved therapy.

Detailed Description:

Patients with liver cirrhosis will be randomly divided into three groups. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group. The catheter will be inserted to proper hepatic artery. After the catheter placement confirmed by angiography, umbilical cord MSCs will be infused slowly in 20-30 minutes. Umbilical cord MSCs will be infused intravenously slowly in 30-60 minutes in the intravenous infusion group. The control group will receive conserved therapy. The levels of serum alanine aminotransferase (ALT), total bilirubin (TB), prothrombin time (PT), prealbumin(PA)and albumin (ALB) will be examined at re-transplantation, and 3 days to 2 years post-transplantation. The efficacy of umbilical cord MSCs transfusion will be investigated. The efficacy of different interventional therapies will also be compared.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-70 years.
Imaging evidences of liver cirrhosis.
Child-Plough score of 8 or more.
Model for End-Stage Liver Disease score of 20 or more.

Exclusion Criteria:

Liver tumor on ultrasonography, CT or MRI examination.
Problems in organs other than liver (e.g. heart or lungs).
History of moderate to severe hepatic encephalopathy or variceal bleeding.
Imaging evidences of vascular thromboses.
Coma.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01233102

Contacts

Contact: Jianhe Gan, MD	86-0512-67780667	ganjianhe@yahoo.com
Contact: Yufang Shi, PhD, DVM	86-21-63848329	yufangshi@sibs.ac.cn

Locations

China, Jiangsu
First Affiliated Hospital of Soochow University	Recruiting
Suzhou, Jiangsu, China, 215006
Contact: Jianhe Gan, MD

Sponsors and Collaborators

Chinese Academy of Sciences

Soochow University

Investigators

Principal Investigator:	Yufang Shi, PhD,DVM	Chinese Academy of Sciences
Study Chair:	Jianhe Gan, MD	The First Affiliated Hospital of Soochow University

More Information

Publications:

Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008 Feb 7;2(2):141-50.

Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006 Oct;24(10):2292-8. Epub 2006 Jun 15.

Kharaziha P, Hellström PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol. 2009 Oct;21(10):1199-205.

Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res. 2009 Jan;2(1):16-25. Epub 2008 Aug 6. Review.

Abdel Aziz MT, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Ahmed HH, Rashed LA, Sabry D, Hassouna AA, Hasan NM. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem. 2007 Aug;40(12):893-9. Epub 2007 May 3.

Li C, Kong Y, Wang H, Wang S, Yu H, Liu X, Yang L, Jiang X, Li L, Li L. Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis. J Hepatol. 2009 Jun;50(6):1174-83. Epub 2009 Mar 29. Erratum in: J Hepatol. 2009 Nov;51(5):973.

Kim TH, Kim JK, Shim W, Kim SY, Park TJ, Jung JY. Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI. Magn Reson Imaging. 2010 Sep;28(7):1004-13.

Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvand H. Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int. 2010 Apr 27;34(6):601-5.

Responsible Party:	Yufang Shi,PhD., Institue of Health and Science, Chinese Academy of Sciences
ClinicalTrials.gov Identifier:	NCT01233102 History of Changes
Other Study ID Numbers:	SIBS-IHS-20101010, 2010CB945600
Study First Received:	October 25, 2010
Last Updated:	November 2, 2010
Health Authority:	China: Ministry of Health

Keywords provided by Chinese Academy of Sciences:

liver Cirrhosis
Mesenchymal stem cells
Hepatic artery infusion
Intravenous infusion

Additional relevant MeSH terms:

Liver Cirrhosis
Fibrosis
Liver Diseases
Digestive System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on June 18, 2013