Safety and Efficacy of Human Mesenchymal Stem Cells for Treatment of Liver Failure

Liver Failure Clinical Trial

Official title:

Phase Ⅰ/Ⅱ Study of Human Umbilical Cord Derived Mesenchymal Stem Cells (UC-MSCs) for Treatment of Liver Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01218464
• Other study ID #: Beijing302-003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: October 8, 2010
• Last updated: May 30, 2013
• Start date: March 2009
• Est. completion date: March 2014

Study information

• Verified date: May 2013
• Source: Beijing 302 Hospital
• Contact: Fu-Sheng Wang, Professor
• Phone: 86-10-63879735
• Email: fswang[@]public.bta.net.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Failure
• Mesenchymal Stem Cells

Intervention

Drug:
• Conventional plus MSC treatment
Participants received conventional treatment and taken i.v., once per 4 week, at a dose of 0.5*10E6 MSC/kg body for 12 weeks.
• Conventional plus pacebo treatment
Participants received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.

Locations

Country	Name	City	State
China	Beijing 302 Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing 302 Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View Citation

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 — View 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. — View 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. Ar — View 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. Epub 2006 Jun 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The levels of serum Total Protein and Albumin		2 years after treatment	No
Secondary	The levels of serum Total Bilirubin and Direct Bilirubin		2 years after treatment	No
Secondary	The levels of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Cholinesterase (CHE)		2 years after treatment	No
Secondary	The level of alpha-fetoprotein (AFP)		2 years after treatment	No
Secondary	The content of ascites		2 years after treatment	No
Secondary	Survival rate and time		2 years after treatment	No
Secondary	Body temperature, tetter and allergy		Between 0 to 24 hours after UC-MSCs transfusion	Yes
Secondary	The levels of Prothrombin Activity (PA) and Prothrombin Time (PT)		2 years after treatment	No
Secondary	The score for Model for End-Stage Liver Disease		2 years after treatment	No