Evaluation Safety and Efficacy of Umbilical Cord Derived Mesenchymal Stem Cell (UC -MSC) Transplantation for Children Suffering From Liver Cirrhosis Due to Biliary Atresia: A Matched Control Prospective Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- The change of albumin (Liver function)
研究概览
简要总结
Biliary atresia (BA) is the most frequent cause of chronic cholestasis in neonates, accounting for at least 50% of pediatric liver transplantation. BA incidence is estimated to range from 1:5000 to 1:19000 live births. All patients will die due to complications of liver cirrhosis if the operation is not performed. Recently, mesenchymal stem cell (MSC) transplantation has been found as a promising therapy for liver cirrhosis in adults. Bone marrow-derived stem cell transplantation was also performed successfully for children with BA. Compared to MSC isolation from bone marrow, isolating MSCs from umbilical cord (UC) tissue is a less invasive procedure.
Furthermore, UC-derived MSCs (UC-MSCs) have been demonstrated to be safe and effective for liver cirrhosis in adults and different pediatric diseases, including liver cirrhosis due to primary biliary cirrhosis. The investigators will compare the outcomes of 17 Kasai operated BA patients who receive UC-MSC transplantation to 17 BA patients who only undergo Kasai operation. Two transplantations of UC - MSCs will be performed via the hepatic artery: the first transplant will be performed at baseline, and the second one will be performed 6 months later with a dosage of 1 million MSCs per kg of body weight. The frequency and severity of the adverse events or serious adverse events associated with UC-MSC injection at 72 hours post-injection will be used to assess the safety. The efficacy of the therapy will be measured using Pediatric End-Stage Liver Disease (PELD) score, liver function, and liver biopsy. This study would open a novel cell therapy to improve outcomes of patients with BA.
详细描述
The study protocol was approved by the Vinmec International Hospital Ethics Committee, and National Ethics Committees. The stem cell products are conducted in accordance with (GMP) requirements and Good Clinical Practice (GCP). All patients and primary caregivers will receive a written consent form, a cover letter and a clear explanation of the safety issues, potential risks and benefits, and the procedure involved. Moreover, patients will be provided the updated results related to disease and the study during conducting the study and will be fully funded by the project.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Months 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children diagnosed with liver cirrhosis due to biliary atresia after Kasai's operation
- •From 5 months to 2 years old
- •Weight ≥ 6 kg
- •Patients with manifestation of cirrhosis on liver biopsy during Kasai's operation.
- •Parents or primary caregivers signed the informed consent form.
排除标准
- •Under 6kg or over 2 years old
- •Coagulation disorders
- •Allergy to anesthetic agents
- •Active infections
结局指标
主要结局
The change of albumin (Liver function)
时间窗: up to the 12-month period following treatment
Levels of albumin (g/dL)
The change of total bilirubin (Liver function)
时间窗: up to the 12-month period following treatment
Total bilirubin level (mg/dL)
The change of liver biopsy
时间窗: up to the 12-month period following treatment
change of liver biopsy
The change of PELD scores during study
时间窗: baseline, 3 months, 6 months, 9 months, 12 months
The PELD score is calculated using the following formula: PELD Score = 0.480 \* ln (Bilirubin in mg/dL) + 1.857 \* ln (INR) - 0.687 \* ln (Albumin in g/dL) + 0.436 if the patient is \<1 year old + 0.667 if there growth failure
The change of prothrombin time
时间窗: up to the 12-month period following treatment
Prothrombin time (second)
次要结局
- The number of Adverse Events (AE) and Serious Adverse Events (SAE)(baseline, 3 months, 6 months, 9 months, 12 months (time frame: up to the 12-month period following treatment))