Umbilical Cord Mesenchymal Stem Cells for Patients With Liver Cirrhosis

NCT ID: NCT01220492

Last Updated: 2018-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 266 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2016-04-30

Brief 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.

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.

Conditions

Liver Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

conventional plus MSC treatment

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

conventional plus placebo treatment

Intervention Type: DRUG

received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 8 weeks.

Interventions

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.

Intervention Type: DRUG

conventional plus placebo treatment

received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 8 weeks.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Fu-Sheng Wang

the Institute of Translational hepatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fu-Sheng Wang, Professor

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

Beijing 302 Hospital

Beijing, Beijing Municipality, China

Countries

China

References

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

Reference Type: BACKGROUND

PMID: 18328931 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20495456 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19455046 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17903050 (View on PubMed)

Other Identifiers

beijing302-002

Identifier Type: -

Identifier Source: org_study_id