Clinical trial NCT03945487: Mesenchymal Stem Cells Treatment for Decompensated Liver Cirrhosis
Official title: Safety and Efficacy of Human Unbilical Cord Derived-mesenchymal Stem Cells Treatment for Patients With Decompensated Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Decompensated Liver Cirrhosis
Keywords: liver cirrhosis
mesenchymal stem cells
safety
liver function
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2019-05-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Liver function
timeFrame: 96 weeks
measure: The incidence of serious complications
timeFrame: 96 weeks
Secondary outcomes:
measure: The incidence of adverse events
timeFrame: 96 weeks
measure: Disease-free survival time
timeFrame: 96 weeks
measure: Incidence of hepatocellular carcinoma (HCC) events
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing 302 Hospital
Study officials:
affiliation: Beijing 302 Hospital
name: Fu-Sheng Wang
role: STUDY_CHAIR
References: