Umbilical Cord Mesenchymal Stem Cells for Patients With Liver Cirrhosis

Liver Cirrhosis Clinical Trial

Official title:

Phase 1/2 Study of UC-MSC Treatment for the Evaluation the Efficacy and Safety in Patients With Liver Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01220492
• Other study ID #: beijing302-002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2009
• Est. completion date: April 2016

Study information

• Verified date: August 2018
• Source: Beijing 302 Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Liver cirrhosis (LC) represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and formation of regenerative nodules. The liver transplantation is one of the only effective therapies available to such patients. However, lack of donors, surgical complications, rejection, and high cost are it`s serious problems. The potential for stem cells to differentiate into hepatocytes cells was recently confirmed. Particularly, autologous bone marrow-derived mesenchymal stem cell (BM-MSC) has been demonstrated to decrease MELD score and increase serum albumin in the patients with decompensated liver cirrhosis. Therefore, the investigators propose a hypothesis that umbilical cord-derived MSCs (UC-MSC) can also improve the disease conditions of LC patients, particularly reducing the decompensated conditions in these patients.

Description:

Liver cirrhosis (LC) represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and formation of regenerative nodules. The liver transplantation is one of the only effective therapies available to such patients. However, lack of donors, surgical complications, rejection, and high cost are it`s serious problems.

The potential for stem cells to differentiate into hepatocytes cells was recently confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been applicated in the clinic for treat several human diseases such as GVHD, cardiac injury and brain injury, and displayed good tolerance and efficiency. BM-MSC has also been used to treat human liver diseases such as liver failure and liver cirrhosis. In a phase 1 study, autologous BM-MSC transplantation has potential to decrease MELD score and increase serum albumin in the patients with decompensated liver cirrhosis.

The purpose of this study is to learn whether and how umbilical cord-derived MSCs (UC-MSC) can improve the longer term survival in patients with liver cirrhosis. This study will also look at how well BM-MSC is tolerated and its safety in LC patients.

Participants in the study will be randomly assigned to one of two treatment arms:

Arm A: Participants will receive conserved treatment plus three times UC-MSC treatment at 4-week intervals.

Arm B: Participants will receive conserved treatment plus three times saline infusions at 4-week intervals.

UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anti coagulant. MSCs are infused intravenously. After cell therapy, patients are followed up for 75 months. The evaluation of some clinical parameters such as the level of serum alanine aminotransferase (ALT), total bilirubin (TB),prothrombin time (PT), albumin (ALB), prealbumin(PA), the rountin blood test are detected at week 12, 24, 48 timepoints. Clinical symptoms as well as complication were also observed simultaneously.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Liver cirrhosis

2. Negative pregnancy test (female patients in fertile age)

3. written consent

Exclusion Criteria:

1. Hepatocellular carcinoma or other malignancies

2. Pregnancy

3. sepsis

4. Presence of significant extrahepatic biliary disease (e.g. CBD stone, PSC, etc.)

5. Cardiac, renal or respiratory failure

6. Active thrombosis of the portal or hepatic veins

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• conventional plus MSC treatment
received conventional treatment and taken i.v., once per 4 week, at a dose of 0.5*10E6 MSC/kg body for 8 weeks.
• conventional plus placebo treatment
received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 8 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 (4)

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. doi: 10.1097/MEG.0b013e32832a1f6c. — View Citation

Kisseleva T, Gigante E, Brenner DA. Recent advances in liver stem cell therapy. Curr Opin Gastroenterol. 2010 Jul;26(4):395-402. doi: 10.1097/MOG.0b013e32833a6bec. Review. — 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

Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008 Mar 8;371(9615):838-51. doi: 10.1016/S0140-6736(08)60383-9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival time		75 months
Primary	incidence of HCC events		75 months
Secondary	The levels of serum albumin		48 weeks
Secondary	The levels of serum total bilirubin		48 weeks
Secondary	The levels of serum prothrombin activity		48 weeks
Secondary	the levels of serum cholinesterase		48 weeks
Secondary	complications		48 weeks