Phase I Clinical Trial, Randomized, Controlled, to Evaluate the Efficacy and Safety of Therapy With Allogenic Mesenchymal Stem Cells From Bone Marrow for Patients With Refractory Primary Biliary Cirrhosis
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- serum level of alkaline phosphatase
研究概览
简要总结
The study is designed to evaluate the safety and efficacy of intravenous administration of bone marrow derived mesenchymal stem cells for patients with refractory primary biliary cirrhosis (PBC).
详细描述
Primary biliary cirrhosis (PBC) is an organ-specific inflammatory disease and characterized by immune mediated destruction of intrahepatic bile ducts, then lead to liver cirrhosis and eventually failure.Currently, ursodeoxycholic acid (UDCA) is the only drug approved by the Food and Drug Administration (FDA). Novel treatment is urgently needed for patients who have an incomplete response to UDCA. Mesenchymal stem cells (MSC) represent a promising tool for cell-based therapies of autoimmune diseases. To explore the therapeutic effect of MSCs for PBC, the investigators plan to conduct an open-label, randomized clinical trial. Patients with PBC will be enrolled and randomly divided into two groups which will receive MSCs and UDCA respectively. The investigators will evaluate the efficacy and safety of MSCs for PBC by comparison of symptom improvement, survival rate and side effects in the two groups.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •There must be at least two of the following: a concentration in serum of AMAs at titres of 1:40 or higher; an unexplained rise in the amount of alkaline phosphatase of at least 1•5 times the upper limit of normal for more than 24 weeks; and compatible liver histological findings, specifically non-suppurative cholangitis and interlobular bile duct injury.
- •Incomplete response to UDCA at 13-15 mg/kg/day, Criteria for the group of complete responders is including: concentrations of alkaline phosphatase less than three times the upper limit of normal, aspartate aminotransferase less than twice the upper limit of normal, and bilirubin less than 17 μmol/L;and normalisation of abnormal concentrations of bilirubin, albumin, or both.
- •Liver pathological staging in 2 or3, Histological staging is based on Ludwig's and Scheuer's classifications
排除标准
- •Patients are receiving any other investigational agents within 4 weeks of study entry
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia
- •In pregnancy or lactation
- •Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- •HCVpositive ，HBSAg positive or with other liver diseases
- •Combined with other autoimmune disease
- •Expected survival time is less than one year
- •Decompensation of liver function（Child B or C）
- •Have a history of allergy or Allergic constitution
研究组 & 干预措施
ursodeoxycholic acid (UDCA)
Patients who have primary biliary cirrhosis.
干预措施: ursodeoxycholic acid (Drug)
结局指标
主要结局
serum level of alkaline phosphatase
时间窗: 24 months after MSCs administration
Serum level of alkaline phosphatase will be measured at entry, 1 months，3 months, 6 months and 24 months after therapy
次要结局
- The occurrence of cirrhosis and its complications(24 months after therapy)
- histological changes in liver biopsies(6 months after therapy)
- Serum levels of TNF-alpha(6 months after therapy)
- changes in fatigue(6 months after theraphy)
- Serum levels of Interleukin(6 months after therapy)
- changes in pruritus severity(6 months after therapy)
研究者
Robert Chunhua Zhao, MD, PhD
MD, PhD，Professor of medicine
Chinese Academy of Medical Sciences