Clinical Research of Human Umbilical Cord Mesenchymal Stem Cell Transplantation for The Treatment of Acute-on-Chronic Liver Failure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Transplantation free survival rate
研究概览
简要总结
This study is a randomized double-blind placebo-controlled multicenter clinical trial to evaluate the safety and efficacy of human umbilical cord mesenchymal stem cell (UC-MSC) transplantation for the treatment of acute-on-chronic liver failure (ACLF). UC-MSC therapy may improve the clinical outcomes of patients with ACLF. The trial would provide scientific evidence for UC-MSC transplantation as a potential treatment for ACLF.
详细描述
Acute-on-chronic liver failure (ACLF) has been proposed to define a distinct syndrome which is characterized by an intense systemic inflammatory response, single- or multiple organ system failures, and high 28-day mortality. Current treatments for liver failure are still limited, and liver transplantation remains the only available approach to improve survival but is restricted by a shortage of organ resources, rejection after transplantation, and heavy financial costs. In the past decade, a series of new applications based on mesenchymal stem cell (MSC) therapy have been studied as an alternative interventional method for chronic liver diseases. This randomized double-blind placebo-controlled multicenter clinical trial is aimed at determining the safety and clinical efficacy of UC-MSC transfusions in ACLF patients.
A total of 150 ACLF patients would be enrolled,100patients would be assigned to the MSC intervention group and the other 50 patients would be assigned to the placebo control group. This trial is two-stage randomized designed. At the first stage, the patients would be randomized into two groups, the placebo short control group would receive standard medical treatment plus 3 times placebo (at week0, week1 and week2), while the MSC short treatment group would receive standard medical treatment plus 3 times hUC-MSC (1.5×10^8, Peripheral IV, at week0, week1 and week2). The two groups would be followed up for 2 weeks, and unblinding would be conducted at week4. At the second stage, the survived patients of the MSC short treatment group would be further randomized and blinded into another two groups. The MSC Prolonged treatment group would receive another 2 times hUC-MSC (1.5×10^8, Peripheral IV, at week4 and week5), while the MSC Prolonged control group would receive 2 times placebo (at week4 and week5).
Transplantation free survival rate and incidence of treatment-emergent adverse events would be the primary outcomes, and other outcomes such as international normalized ratio (INR), total bilirubin (TBIL, mg/dL), serum albumin (ALB, g/L), blood urea nitrogen (BUN, mmol/l), the model for end-stage liver disease(MELD) score and child-turcotte-pugh(CTP) score would also be measured.
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
- Double (Participant, Investigator)
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
- •18 years old ≤ age ≤ 70 years old, gender is not limited.
- •Meet the APASL definition of ACLF: acute liver injury in patients with previously diagnosed or undiagnosed chronic liver disease or cirrhosis, manifested as jaundice (total bilirubin levels of 5 mg/dl or more) and coagulopathy (INR of 1.5 or more, or prothrombin activity of less than 40%） complicated within 4 weeks by clinical ascites, encephalopathy, or both.
- •Willing to sign the informed consent form.
排除标准
- •Patients with acute kidney injury, upper gastrointestinal hemorrhage, hepatic encephalopathy above grade II (inclusive) or uncontrolled infection at baseline;
- •Before the onset of liver failure, the previous indicators of the patient included PLT<50×10^9/L or Child-Pugh score>9;
- •Combined with liver cancer or other malignant tumors;
- •Patients with previous liver transplantation or planned liver transplantation within 3 months;
- •Severe organic disease of primary extrahepatic organs;
- •Those who have a history of venous thrombosis or pulmonary embolism are judged by the investigator to be ineligible to participate in this trial;
- •Pregnant, breastfeeding women or those who plan to have a baby in the near future;
- •Those who are highly allergic or have a history of severe allergies;
- •Those who have received immunosuppressant and immune enhancer treatment within 1 month;
- •Drug abuse in the past 5 years;
- •Alcohol withdrawal symptoms;
- •A history of severe mental disorders within 24 months before screening, including uncontrolled major depression or controlled or uncontrolled psychosis;
- •Those who have participated or are participating in other clinical trials within three months before screening, or have previously received stem cell therapy;
- •Other conditions that the investigator thinks that the patient is not suitable to participate in this study.
研究组 & 干预措施
Group Control
standard medical treatment+Placebo(5% human serum albumin in 0.9% saline, at week0, week1 and week2)
干预措施: standard medical treatment (Drug)
Group Control
standard medical treatment+Placebo(5% human serum albumin in 0.9% saline, at week0, week1 and week2)
干预措施: Placebo (Drug)
Group MSC-1
Patients received standard medical treatment and infusions of hUC-MSC(1.5×10^8) via peripheral veins once a week for 3 timess(at week0, week1, and week2).
干预措施: standard medical treatment (Drug)
Group MSC-1
Patients received standard medical treatment and infusions of hUC-MSC(1.5×10^8) via peripheral veins once a week for 3 timess(at week0, week1, and week2).
干预措施: hUC-MSC (Drug)
Group MSC-2
Patients in Group MSC-1 received standard medical treatment and infusions of hUC-MSC(1.5×10^8) via peripheral veins once a week for another 2 timess(at week4 and week5).
干预措施: standard medical treatment (Drug)
Group MSC-2
Patients in Group MSC-1 received standard medical treatment and infusions of hUC-MSC(1.5×10^8) via peripheral veins once a week for another 2 timess(at week4 and week5).
干预措施: hUC-MSC (Drug)
Group MSC-2
Patients in Group MSC-1 received standard medical treatment and infusions of hUC-MSC(1.5×10^8) via peripheral veins once a week for another 2 timess(at week4 and week5).
干预措施: hUC-MSC_Prolonged (Drug)
结局指标
主要结局
Transplantation free survival rate
时间窗: week1, week2, week3, week4, week5, week8, week12, week24, week53
Transplantation free survival rate of ACLF patients.
Incidence of Treatment-Emergent Adverse Events
时间窗: day0, day3, week1, week2, week3, week4, week5, week8, week12, week24, week53
Safety and Tolerability of UC-MSCs transplantation.
次要结局
- International Normalized Ratio (INR)(week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53)
- Concentration of Total Bilirubin (TBIL, mg/dL)(week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53)
- Concentration of Serum Albumin (ALB, g/L)(week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53)
- Concentration of Blood Urea Nitrogen (BUN, mmol/L)(week-1, week0, day3, week1, week2, week3, week4, week5, week12, week24, week53)
- The Model for End-Stage Liver Disease(MELD) score(week-1, week1, week2, week4, week5, week12, week24, week53)
- Child-Turcotte-Pugh(CTP) score(week-1, week1, week2, week4, week5, week12, week24, week53)
研究者
Shi Ming
Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases
Beijing 302 Hospital