Mesenchymal Stem Cells Treatment for Decompensated Liver Cirrhosis

NCT ID: NCT03945487

Last Updated: 2019-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2023-12-30

Brief Summary

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.

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.

Conditions

Decompensated Liver Cirrhosis

Study Design

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

Study Groups

Comprehensive treatment plus UC-MSC treatment

Group Type: EXPERIMENTAL

umbilical cord-derived mesenchymal stem cell

Intervention Type: BIOLOGICAL

Taken a dose of 1.0\*10E6 UC-MSC/kg body weight intravenously three times at 3-week intervals, in addition to comprehensive treatment.

Comprehensive treatment

Group Type: OTHER

Comprehensive treatment

Intervention Type: OTHER

1. All patients received anti-HBV treatment with NAs (entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)).

2. 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).

Interventions

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.

Intervention Type: BIOLOGICAL

Comprehensive treatment

1. All patients received anti-HBV treatment with NAs (entecavir (ETV), tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)).

2. 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).

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Fu-Sheng Wang

Treatment and Research Center for Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fu-Sheng Wang

Role: STUDY_CHAIR

Beijing 302 Hospital

Locations

Beijing 302 Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Ming Shi

Role: CONTACT

shiming302@sina.com

86-10-63879735

Facility Contacts

Ming Shi

Role: primary

Other Identifiers

Beijing302-011

Identifier Type: -

Identifier Source: org_study_id