Umbilical Cord Mesenchymal Stem Cells for Patients With Liver Cirrhosis

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: conventional plus MSC treatment; Drug: conventional plus placebo treatment

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 266
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100039
      • Beijing 302 Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: conventional plus MSC treatment; participants will receive conventional treatment plus a dose of MSC from day 0 through the week 8 study visit. Participants will then be followed until the 75 months study visit.	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.
Experimental: conventional plus placebo treatment; participants will receive conventional plus placebo treatment from day 0 through the week 8 study visit. Participants will then be followed until the 75 months study visit.	Drug: conventional plus placebo treatment; received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
survival time	75 months
incidence of HCC events	75 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The levels of serum albumin	48 weeks
The levels of serum total bilirubin	48 weeks
The levels of serum prothrombin activity	48 weeks
the levels of serum cholinesterase	48 weeks
complications	48 weeks

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital

Publications and helpful links

General Publications

• 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.
• Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008 Mar 8;371(9615):838-51. doi: 10.1016/S0140-6736(08)60383-9.
• 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.
• 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. Erratum In: Arch Iran Med. 2008 Jan;11(1):135.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2009
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: October 4, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 14, 2010

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: safety; mesenchymal stem cells; liver cirrhosis; longer term survival
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: beijing302-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No