Clinical trial NCT01233102: Mesenchymal Stem Cells Treat Liver Cirrhosis
Official title: Umbilical Cord Mesenchymal Stem Cell Transfusion in Patients With Severe Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Liver Cirrhosis
Keywords: liver Cirrhosis
Mesenchymal stem cells
Hepatic artery infusion
Intravenous infusion
Lead sponsor: Chinese Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: Soochow University
First posted: 2010-11-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: The level of serum alanine aminotransferase (ALT）
timeFrame: 1 year
measure: The level of serum total bilirubin (TB)
timeFrame: 1 year
measure: The level of serum prothrombin time (PT)
timeFrame: 1 year
measure: The level of serum prealbumin(PA)
timeFrame: 1 year
measure: The level of serum albumin (ALB)
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Secondary outcomes:
measure: liver biopsy
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: The level of serum alanine aminotransferase (ALT）
timeFrame: 2 years
measure: The level of serum total bilirubin (TB)
timeFrame: 2 years
measure: The level of serum prothrombin time (PT)
timeFrame: 2 years
measure: The level of serum albumin (ALB)
timeFrame: 2 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: Chinese Academy of Sciences
name: Yufang Shi, PhD,DVM
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Soochow University
name: Jianhe Gan, MD
role: STUDY_CHAIR
References:
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citation: 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. doi: 10.1016/j.clinbiochem.2007.04.017. Epub 2007 May 3.
citation: 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. doi: 10.1016/j.jhep.2009.01.028. Epub 2009 Mar 29.
citation: 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. doi: 10.1016/j.mri.2010.03.047.
citation: 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. doi: 10.1042/CBI20090386.