A Phase 1 Dose Escalation Study of Human Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment of Decompensated Cirrhosis (MSC-DLC-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
研究概览
简要总结
This is a Phase 1, open label, dose escalation clinical trial of human umbilical cord-derived mesenchymal stem cells for the treatment of decompensated cirrhosis. The purpose of this study is to assess the safety of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.
详细描述
The primary objective of this study is to assess the safety of intravenous infusion of human umbilical cord-derived mesenchymal stem cells in patients with decompensated cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing to provide written informed consent;
- •Aged 18 to 75 years (including 18 and 75 years), male or female;
- •Patients diagnosed with decompensated liver cirrhosis based on clinical findings, laboratory tests, imaging findings and/or representative pathological findings (decompensated liver cirrhosis is defined as the occurrence of at least one serious complication, including esophageal and gastric varices bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis and other serious complications);
- •Child-Turcotte-Pugh (CTP) score 7 to 12 points.
排除标准
- •Appearance of active variceal bleeding, overt hepatic encephalopathy (HE), refractory ascites or hepatorenal syndrome within 1 month prior to screening visit.
- •Uncontrolled severe infection within 2 weeks of screening.
- •Hepatitis B virus (HBV) DNA ≥ detection limit at the time of screening.
- •Patients with hepatitis B virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HBV for less than 12 months.
- •Patients with hepatitis C virus-related decompensated liver cirrhosis may discontinue antiviral therapy during the study, or those who with antiviral therapy for HCV for less than 12 months.
- •Patients under treatment with corticosteroids for autoimmune hepatitis for less than 6 months.
- •Trans-jugular intrahepatic portosystemic shunts (TIPS) insertion within 6 months prior to study inclusion.
- •Active drinkers with alcohol-related decompensated cirrhosis are unwilling to stop alcohol abuse after inclusion.
- •Severe jaundice (serum total bilirubin level ≥ 170μmol/L); Significant renal insufficiency (serum creatinine ≥ 1.2 times upper normal limit); Severe electrolyte abnormality (serum sodium level < 125 mmol/L); Severe leukopenia (white blood cell count < 1 × 10E9/L).
- •Patients with biliary obstruction, hepatic vein, portal vein, splenic vein thrombosis and portal vein spongiosis.
- •Patients with surgical history such as splenic cut-off flow and portal body shunt.
- •Patients with confirmed or suspected malignancies.
- •Patients with a prior history of major organ transplantation or complicated with significant disease of heart, lung, kidney, blood, endocrine and other systems.
- •Drug abuse, drug dependence and patients who receive methadone treatment or with psychosis.
- •HIV seropositivity.
- •Those who have received blood transfusion or other blood products within 1 month prior to screening visit.
- •Pregnancy, lactation or with recent fertility plan.
- •Highly allergic or have a history of severe allergies.
- •Participants in other clinical trials within the last 3 months.
- •Any other clinical condition which the investigator considers would make the patient unsuitable for the trial.
结局指标
主要结局
Change in Model for End-Stage Liver Disease (MELD) score from baseline to 28th day
时间窗: at 28th day
The Model for End-stage Liver Disease (MELD) is a scoring system that evaluates the liver function reserve and prognosis of patients with chronic liver disease by creatinine, international normalized ratio (INR), and bilirubin-conjugated cirrhosis etiology. The MELD score is calculated by the formula: R = 9.6 × ln (creatinine mg/dl) + 3.8 × ln (bilirubin mg/dl) + 11.2 × ln (INR) + 6.4 × etiology, and the results are taken as integers. ( 0 for cholestatic and alcoholic cirrhosis and 1 for other causes of cirrhosis such as viruses).
Incidence of Adverse Events Incidence of Adverse Events
时间窗: from baseline to 28th day
次要结局
- Incidence of each complication associated with decompensated cirrhosis(up to 24 months)
- Change in Model for End-Stage Liver Disease (MELD) score from baseline to 3 days, 7days, 14 days, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months(3 days, 14 days, 3 months, 6 months, 9 months, 12 months, 15 months, 18 months, 21 months, and 24 months)
- liver transplant-free survival(up to 24 months)
- Incidence of liver failure(up to 24 months)
- plasma albumin (ALB)(up to 24 months)
- plasma prealbumin (PALB)(up to 24 months)
- total bilirubin (TBIL)(up to 24 months)
- serum cholinesterase (CHE)(up to 24 months)
- prothrombin time (PT)(up to 24 months)
- Child-Turcotte-Pugh (CTP) score(up to 24 months)
- EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D)(up to 24 months)
- Incidence of liver cancer(up to 24 months)
- ChronicLiver Disease Questionnaire (CLDQ)(up to 24 months)
研究者
Fu-Sheng Wang
Head of Treatment and Research Center for Infectious Diseases, Principle Investigator, Clinical Professor
Beijing 302 Hospital