Umbilical Cord Mesenchymal Stem Cells for Patients With Liver Cirrhosis

Beijing 302 Hospital

Status and phase: Completed; Phase 2; Phase 1

Conditions: Liver Cirrhosis

Treatments: Drug: conventional plus placebo treatment; Drug: conventional plus MSC treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT01220492

beijing302-002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 266 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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266 participants in 2 patient groups

conventional plus MSC treatment

Experimental group

Description:

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.

Treatment:

Drug: conventional plus MSC treatment

conventional plus placebo treatment

Experimental group

Description:

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.

Treatment:

Drug: conventional plus placebo treatment