Clinical trial NCT01220492: Umbilical Cord Mesenchymal Stem Cells for Patients With Liver Cirrhosis
Official title: Phase 1/2 Study of UC-MSC Treatment for the Evaluation the Efficacy and Safety in Patients With Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Liver Cirrhosis
Keywords: liver cirrhosis
mesenchymal stem cells
longer term survival
safety
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2010-10-14
Enrollment: 266
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: survival time
timeFrame: 75 months
measure: incidence of HCC events
timeFrame: 75 months
Secondary outcomes:
measure: The levels of serum albumin
timeFrame: 48 weeks
measure: The levels of serum total bilirubin
timeFrame: 48 weeks
measure: The levels of serum prothrombin activity
timeFrame: 48 weeks
measure: the levels of serum cholinesterase
timeFrame: 48 weeks
measure: complications
timeFrame: 48 weeks
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: Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008 Mar 8;371(9615):838-51. doi: 10.1016/S0140-6736(08)60383-9.
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.
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.
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.