Clinical trial NCT01218464: Safety and Efficacy of Human Mesenchymal Stem Cells for Treatment of Liver Failure
Official title: Phase Ⅰ/Ⅱ Study of Human Umbilical Cord Derived Mesenchymal Stem Cells (UC-MSCs) for Treatment of Liver Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Liver Failure
Mesenchymal Stem Cells
Keywords: Liver Failure
Mesenchymal Stem Cells
Model for End-Stage Liver Disease
Ascite
Serum Albumin
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2010-10-11
Enrollment: 70
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: Liver failure (LF) is a dramatic clinical syndrome with massive necrosis of liver cells. and liver transplantation is the only available therapeutic option for patients suffering with this condition. However, lack of donors, surgical complications, rejection, and high cost are serious problems. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs) replace hepatocytes in injured liver, and effectively rescue experimental liver failure and contribute to liver regeneration. In this study, the patients with LF will undergo administration of human umbilical cord mesenchymal stem cells (UC-MSCs) via peripheral vein transfusion to evaluate the safty and efficacy of UC-MSCs treatment for these patients.

Detailed description: Liver failure (LF) is a severe life-threatening condition, and is a dramatic clinical syndrome with massive necrosis of liver cells, and liver transplantation is the only available therapeutic option for patients suffering with this condition. However, lack of donors, surgical complications, rejection, and high cost are serious problems. Since current therapeutic options for LF that is usually with extremely poor prognosis are still limited, recent studies indicate that mesenchymal stem cells (MSCs), due to their function in immune modulation and liver-damage repair, are of great therapeutic potential for this disease. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs) replace hepatocytes in injured liver, and effectively rescue experimental liver failure and contribute to liver regeneration.The purpose of this study is to investigate the safety and initial efficacy of human umbilical cord MSC (UC-MSCs) treatment for patients with LF. In this study, MSCs were isolated from umbilical cord and generated in appropriate growth medium. 50 LF patients with LF received i.v. transfusion of 0.5-1.0×106 cells/kg of MSCs as the treated group and other 20 LF patients with LF were transfused with placebo without MSCs as control group. All 70 of them received the routine management for liver failure. During the 2-year follow up, the evaluation of safty and efficacy will be undergone to help to establish innovative cell-based therapies for the treatment of diseases.

Eligibility criteria: Inclusion Criteria:

1. Aged 18-70 years
2. Liver failure
3. Negative pregnancy test (female patients in fertile age)
4. Written consent

Exclusion Criteria:

1. Hepatocellular carcinoma or other malignancies
2. Severe problems in other vital organs(e.g.the heart,renal or lungs)
3. Pregnant or lactating women
4. Severe bacteria infection
5. Anticipated with difficulty of follow-up observation
6. Other candidates who are judged to be not applicable to this study by doctors

Primary outcomes:
measure: The levels of serum Total Protein and Albumin
timeFrame: 2 years after treatment
Secondary outcomes:
measure: The levels of serum Total Bilirubin and Direct Bilirubin
timeFrame: 2 years after treatment
measure: The levels of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Cholinesterase (CHE)
timeFrame: 2 years after treatment
measure: The level of alpha-fetoprotein (AFP)
timeFrame: 2 years after treatment
measure: The content of ascites
timeFrame: 2 years after treatment
measure: Survival rate and time
timeFrame: 2 years after treatment
measure: Body temperature, tetter and allergy
timeFrame: Between 0 to 24 hours after UC-MSCs transfusion
measure: The levels of Prothrombin Activity (PA) and Prothrombin Time (PT)
timeFrame: 2 years after treatment
measure: The score for Model for End-Stage Liver Disease
timeFrame: 2 years after treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing 302 Hospital
state: Beijing
Study officials:
affiliation: Beijing 302 Hospital
name: Fu-Sheng Wang, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, Yang VW, Lee OK. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology. 2008 Jun;134(7):2111-21, 2121.e1-3. doi: 10.1053/j.gastro.2008.03.015. Epub 2008 Mar 12.
citation: Campard D, Lysy PA, Najimi M, Sokal EM. Native umbilical cord matrix stem cells express hepatic markers and differentiate into hepatocyte-like cells. Gastroenterology. 2008 Mar;134(3):833-48. doi: 10.1053/j.gastro.2007.12.024. Epub 2007 Dec 23.
citation: 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. doi: 10.1634/stemcells.2005-0542. Epub 2006 Jun 15.
citation: Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, Bagheri M, Bashtar M, Ghanaati H, Baharvand H, Ghavamzadeh A, Malekzadeh R. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med. 2007 Oct;10(4):459-66.
citation: Kharaziha P, Hellstrom 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. doi: 10.1097/MEG.0b013e32832a1f6c.