Mesenchymal Stem Cells-Derived Extracellular Vesicles (MSC-EV) in Acute/Acute-on-Chronic Liver Failure After Liver Transplantationa：a Prospective, Randomized, Controlled Clinical Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.
研究概览
简要总结
Acute liver failure (ALF) refers to a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. Acute-on-chronic liver failure refers to a liver failure syndrome in which some patients with chronic liver disease with relatively stable liver function suffer from acute liver decompensation and liver failure due to the effects of various acute injury factors. Liver transplantation is the only curative treatment for this type of end-stage liver disease. The potential of MSCs to repair or regenerate damaged tissue and suppress immune responses makes them promising in the treatment of liver diseases, especially in the field of liver transplantation. Many studies have shown that MSC-based therapies can reduce the symptoms of liver disease due to their paracrine effects. Therefore, compared to the cells they derive from, mesenchymal stem cells-derived extracellular vesicles (MSC-EV) are gradually gaining attention for their enhanced safety, as they do not replicate or cause microvascular embolism, and can be easily stored without losing their properties. It represents a novel and effective cell-free therapeutic agent as alternative to cell-based therapies for liver diseases, and liver failure was also concerned. This study was designed to evaluate the safety and tolerability of MSC-EV in acute-on-chronic liver failure after liver transplantation.
详细描述
In the MSC-EV group (experimental group), 15 patients will receive a single injection of MSC-EV after their first liver transplantation. In the non-MSC-EV group (control group), 15 patients will not receive MSC-EV therapy after their first liver transplantation.
The outcome of the experimental group will be compared with that of similar control patients undergoing liver transplantation but who will not receive MSC-EV. Both of the two groups will receive standard immunosuppressive therapy( a regimen based on tacrolimus (TAC), mycophenolate mofetyl (MMF) and steroids). Patients participated in the experimental cohort will be infused with a single dose of 10 E10 MSC-EV particles per 100ml, at an appropriate time during the first 1-5 days after transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged 18-70 years;
- •Acute on chronic liver failure-which is characterized by acute hepatic insult manifesting as jaundice (serum total bilirubin [TBil] ≥ 10×ULN umol/L) and coagulopathy (international normalized ratio [INR] ≥ 1.5 or prothrombin activity < 40%), complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination, in patients with previously diagnosed or undiagnosed chronic liver disease; Requiring liver transplantation due to acute on chronic liver failure;
- •Obtain the patients' consent after informing patients of the purpose and method of the clinical trial;
排除标准
- •Past history of malignant disease
- •Active uncontrolled infection;
- •Combined transplantation
- •EBV-negative;
- •HIV or HCV positive;
- •Retransplantation;
研究组 & 干预措施
MSC-EVs group
After liver transplantation, on the basis of postoperative standard treatment (anti-infection treatment, immunosuppressive treatment, nutritional support treatment, etc.), an additional injection of MSC-EV will be received between the 1st and 5th days after transplantation
干预措施: MSC-EVs (Biological)
结局指标
主要结局
Number of participants with MSC-EV infusion-related toxicity as assessed by CTCAE v4.0.
时间窗: 24 hours after injection
Incidence, timing and severity of any clinical complication related to MSC-EV infusion, such as tympanic body temperature, heart rate, mean arterial blood pressure and allergy, as assessed by CTCAE v4.0 .
Aspartate aminotransferase (AST)
时间窗: 6 months after transplantation
Collect clinical results reflecting liver function
Alanine aminotransferase (ALT)
时间窗: 6 months after transplantation
Collect clinical results reflecting liver function
Bilirubin level
时间窗: 6 months after transplantation
Collect clinical results reflecting liver function
International normalized ratio (INR)
时间窗: 6 months after transplantation
Collect clinical results reflecting liver function
carbohydrate Compound antigen (GGT) level
时间窗: 6 months after transplantation
Collect clinical results reflecting liver function
Adverse events
时间窗: 6 months after transplantation
Any adverse events which may related to MSC-EV infusion
次要结局
- Number of survived patients at 1 year after liver transplantation, according to the follow-up results.(12 months)
- Number of survived grafts at 1 year after liver transplantation, according to the follow-up results.(12 months)
- Recipient's immune function, as assessed by analysis of immune cell subsets from biopsy or blood samples ,at months 1-6 after liver transplantation.(6 months after transplantation)
研究者
Jun Zheng
Doctor of Department of Hepatic Surgery and Liver Transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University
Third Affiliated Hospital, Sun Yat-Sen University