Mesenchymal Stem Cells Treatment for Decompensated Liver Cirrhosis

Safety and Efficacy of Human Unbilical Cord Derived-mesenchymal Stem Cells Treatment for Patients With Decompensated Liver Cirrhosis

Decompensated liver cirrhosis is a life-threatening chronic liver disease with high mortality. Liver transplantation is the only option that can improve the survival of these patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists, multiple complications, and high cost. Our and other previous studies have demonstrated that marrow bone-derived mesenchymal stem cells (BM-MSC) or unbilical cord derived MSC (UC-MSC) infusion is clinically safe and could improve liver function in patients with decompensated liver cirrhosis. However, the long-term outcomes of MSC infusion have not been reported until now. This prospective and randomized controlled study examined the longer-term safety and efficacy of UC-MSC in patients with decompensated liver cirrhosis.

Study Overview

• Status: Recruiting
• Conditions: Decompensated Liver Cirrhosis
• Intervention / Treatment: Biological: umbilical cord-derived mesenchymal stem cell; Other: Comprehensive treatment

Detailed Description

Liver cirrhosis represents a late stage of progressive hepatic fibrosis characterized by the formation and accumulation of an extracellular matrix, which leads to the progressive distortion of the hepatic architecture. In China, the most important cause of liver cirrhosis is chronic hepatitis B virus (HBV) infection. Liver cirrhosis usually progresses irreversibly into advanced stage, such as a decompensated stage which is characterized by a series of clinical manifestations, including ascites, variceal hemorrhage, and hepatic encephalopathy with high mortality. Liver transplantation is the only option that can improve the survival of these decompensated liver cirrhosis patients; however, this procedure is associated with several limitations, such as the severe shortage of donor livers, long waiting lists, multiple complications, and high cost. Therefore, it is urgent to find a safe and effective therapeutic approach to decompensated liver cirrhosis.

Animal models have shown that bone marrow-derived MSC (BM-MSC) can ameliorate liver fibrosis and reverse fulminant hepatic failure. In clinical, autologous BM-MSC have significantly improved liver function in patients with liver cirrhosis. A recent research also found that autologous BM-MSC therapy safely improved histological fibrosis and liver function in patients with alcoholic cirrhosis. Allogeneic MSC therapy, such as umbilical cord-derived MSC (UC-MSC), have shown to be safe and beneficial for the patients with liver cirrhosis caused by autoimmune diseases. Our previous studies showed that infusions of UC-MSC significantly improved liver function in decompensated liver cirrhosis and primary biliary cirrhosis (PBC) patients and increased the survival rate in acute-on-chronic liver failure (ACLF) patients. However, the single-center clinical study, the relative small size of the patient cohorts, absence of evaluation on long-term efficacy prevent firm conclusions being made with regard to the safety and efficacy of this treatment in liver diseases.

The purpose of this study is to investigate whether and how UC-MSC can improve the liver function, and the incidence of serious complications in patients with decompensated liver cirrhosis through a multi-center clinical study.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100039
    • Recruiting
    • Beijing 302 Hospital
    • Contact: Ming Shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-69 years;
2. Decompensated liver cirrhosis (manifestations including gastrointestinal bleeding, hepatic encephalopathy, and ascites, based on previously stable cirrhosis);
3. Positive testing for serum hepatitis B surface antigen (HBsAg) for more than 6 months (chronic hepatitis B patients);
4. Written consent.

Exclusion Criteria:

1. Hepatocellular carcinoma or other malignancies;
2. Liver cirrhosis caused by other reasons, such as autoimmune diseases, alcocal, drugs and so on;
3. Pregnant women;
4. The presence of other vital organ severe dysfunction;
5. Participate in other studies;
6. Lack of a supportive family;
7. Refusal to sign the informed consent form.

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: Comprehensive treatment plus UC-MSC treatment	Biological: umbilical cord-derived mesenchymal stem cell; Taken a dose of 1.0*10E6 UC-MSC/kg body weight intravenously three times at 3-week intervals, in addition to comprehensive treatment.
Other: Comprehensive treatment	Other: Comprehensive treatment; All patients received anti-HBV treatment with NAs (entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)).; Strategies based on targeting abnormalities in gut-liver axis by antibiotic administration (i.e. rifaximin), improving the disturbed systemic circulatory function (i.e. longterm albumin administration), decreasing the inflammatory state (i.e. statins), and reducing portal hypertension (i.e. beta-blockers).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver function	including the levels of albumin [ALB], prothrombin activity [PTA], total bilirubin [TBIL, and cholinesterase [CHE].	96 weeks
The incidence of serious complications	including infection, gastrointestinal bleeding, encephalopathy, and hepatorenal syndrome.	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse events	e.g. fever, allergy, rash, infection	96 weeks
Disease-free survival time	The length of survival time after first UC-MSC treatment for the patient during the follow-up period.	96 weeks
Incidence of hepatocellular carcinoma (HCC) events	HCC deveopled in the patient during the follow-up period.	96 weeks

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Investigators: Study Chair: Fu-Sheng Wang, Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 20, 2019
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: safety; mesenchymal stem cells; liver cirrhosis; liver function
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: Beijing302-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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