Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- survival rate
研究概览
简要总结
Safety and Efficacy of Mesenchymal Stem Cell Transplantation for Acute-on-Chronic Liver Failure
详细描述
Acute-on-chronic liver failure (ACLF) which occurs in patients with chronic liver disease, is a serious live-threatening disease. Currently, the clinical management, such as liver protection, anti-virus medicine, and artificial liver support, has not significantly improve the outcomes, the mortality still remains over 50%. Liver transplantation is the only effective treatment of ACLF, but this therapy is limited by the shortage of donor organs, potential surgical complications, immunological rejection and high medical costs. Mesenchymal stem cell (MSC) is one of adult stem cells, which has been suggested to play a role in amelioration of liver disease, such as: trans-differentiation of MSCs into hepatocytes, immunomodulation, inhibition of fibrosis development, protective effects on hepatic cell and restoration of hepatic cell proliferation capacity.
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
盲法说明
both participants and the study team are unblinded to the treatment allocation
入排标准
- 年龄范围
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent
- •Meeting the definition of ACLF: patients with previously diagnosed or undiagnosed chronic liver disease acute decompensated within 4 weeks; significant GI symptom as such fatigue, jaundice; serum total bilirubin [TBil] ≥10 X the upper limit of normal; coagulopathy (international normalized ratio [INR] ≥1.5 or prothrombin activity [PTA] <40%); complicated within 4 weeks by ascites and/or encephalopathy as determined by physical examination.
- •Model for End-Stage Liver Disease (MELD) scores ranging 17-30, (MELD(i) = 0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643);
- •Chronic liver disease with definitive etiology such as viral hepatitis, alcohol liver disease, drug induced liver injury or autoimmune liver diseases
- •Body weight ≥50kg
排除标准
- •Serious complications in the previous 2 months (e.g., gastrointestinal bleeding: hemoglobin below 90g/L, serious infection such as sepsis, ascites ultrafiltration, and/or dialysis);
- •Malignant jaundice induced by obstructive jaundice or hemolytic jaundice;
- •Hepatocellular carcinoma (HCC) diagnosed by radiologic imaging and/or alpha fetoprotein (AFP);
- •Tumor diagnosed by ultrasound, CT, MR examination;
- •Moderate or severe chronic heart failure (NYHA III-IV), renal replacement therapy, severe chronic pulmonary disease (GOLD III-IV)
- •Extrahepatic cholestasis
- •Hepatic, portal and splenic vein thrombosis diagnosed by doppler ultrasound
- •Artificial liver support
- •Previous liver transplantation
- •Drug abuse in the past 5 years;
- •Mental disorders and/or has a family history of mental disorder.
- •HIV infection
- •Pregnant or breast-feeding females
- •Highly allergic
- •Patients can not cooperate or mobility
- •Enrolled in other clinical trials with 3 months
- •Patients who can not provide prior informed consent or refusal to participate
研究组 & 干预措施
Mesenchymal Stem Cell
Mesenchymal Stem Cell (MSC): The MSC group received infusions of 1.0 to 10x10^5cells/kg MSCs through the peripheral vein once a week for 4 weeks, in addition to SMT.
干预措施: Mesenchymal Stem Cell (Biological)
Standard Medical Treatment
Standard Medical Treatment (SMT): All patients received SMT, including nutritional supplementation; administration of human serum albumin (serum albumin <30 g/L), fresh frozen plasma (200-400 mL/day until the INR was <1.5), S-adenosylmethionine (1.0 g/day); or anti-virus treatment for hepatic viruses-related cases, and appropriate treatment for complications such as infections (including of the respiratory tract, urinary tract, biliary tract, and digestive tract and spontaneous peritonitis), encephalopathy, gastrointestinal bleeding, and hepatorenal syndrome [HRS]).
结局指标
主要结局
survival rate
时间窗: 72 weeks after treatment
Number of participants alive
次要结局
- Adverse reactions(Week 1, 2, 4, 8, 12, 24, 36, 48)
- ALB(Week 1, 2, 4, 8, 12, 24, 36, 48)
- Liver failure-associated serious complications(Week 1, 2, 4, 8, 12, 24, 36, 48)
- White blood cell(Week 1, 2, 4, 8, 12, 24, 36, 48)
- Platelet(Week 1, 2, 4, 8, 12, 24, 36, 48)
- Hemoglobin(Week 1, 2, 4, 8, 12, 24, 36, 48)
- Creatinine(Week 1, 2, 4, 8, 12, 24, 36, 48)
- TBil(Week 1, 2, 4, 8, 12, 24, 36, 48)
- ALT(Week 1, 2, 4, 8, 12, 24, 36, 48)
- AFP(Week 1, 2, 4, 8, 12, 24, 36, 48)
- Tumor formation(Week 1, 2, 4, 8, 12, 24, 36, 48)
- INRs(Week 1, 2, 4, 8, 12, 24, 36, 48)
- MELD scores(Week 1, 2, 4, 8, 12, 24, 36, 48)