Autologous Endothelial Progenitor Cell Therapy for Reversal of Liver Cirrhosis
试验速览
- 阶段
- 3 期
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Improvement of liver fibrosis on MRE (magnetic resonance elastography)
研究概览
简要总结
This proposal translates a hypothesis driven basic research into clinical setting to determine the potential of using autologous CD133+ cells to reverse fibrosis and improve clinical outcome for patients with end stage cirrhosis. This has significant impact on the management of cirrhosis.
详细描述
This is a 2 arm randomised study patients with decompensated liver cirrhosis involving minimum of 23 and maximum of 33 patients in each arm.
The investigators propose that transplantation of mobilized autologous CD133+ cells harvested from the bone marrow directly into the liver has the ability to replace and regenerate the damaged sinusoidal endothelium as well as normalize macrophage and Natural Killer (NK) cell function. The niche provided by the refenestrated endothelium can polarize the macrophage to antifibrotic phenotype as well as directly inactivate the activated myofibroblast, resulting in reversal of liver fibrosis and improvement in liver function. Transplantation of cells will be via intraportal route delivered by percutaneous cannulation of the portal vein system.
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
- Single (Outcomes Assessor)
盲法说明
Blinding will be maintained by investigators performing analysis of the results. Given the invasive procedure of percutaneous transhepatic cannulation, the investigators felt that it will be unethical to perform sham procedure on control arm patients. Both managing doctors and patient will know which arm they are on but where not inevitable, data collection such as quality of life and results interpretation such as histology and laboratory analysis of results will be performed anonymously.
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver cirrhosis of any aetiology but where active disease is controlled
- •Childs A/B/C with Child-Pugh score >= 5
- •And either one of the following:
- •MELD score 10-27
- •Clinically significant portal hypertension as evidenced by gastroesophageal varices or ascites
排除标准
- •MELD score >27
- •History of hematological or hepatic malignancy within 5 years from consent
- •Other underlying malignancy with <1 year survival
- •Presence of systemic diseases that may impact survival within 1 year.
- •Listed for liver transplant
研究组 & 干预措施
Treatment
Patient will undergo CD133+ cells transplantation at stable compensated state.
5 dose GCSF will be administered 5 days consecutively before bone marrow harvesting.
Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system.
Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins.
干预措施: GCSF (Drug)
Treatment
Patient will undergo CD133+ cells transplantation at stable compensated state.
5 dose GCSF will be administered 5 days consecutively before bone marrow harvesting.
Approximately 250ml of bone marrow will be harvested and subjected to CD133 isolation using clinimacs (Miltenyi Biotec) in a closed system.
Under ultrasound guidance, 50 mls of 50-100 million CD133 cells will be infused directly through transhepatic route into portal venous circulation of the liver over 5 mins.
干预措施: CD133 Cells Transplantation (Procedure)
Control
Non-Transplant Arm:
Patients will receive 5 doses of GCSF
干预措施: GCSF (Drug)
结局指标
主要结局
Improvement of liver fibrosis on MRE (magnetic resonance elastography)
时间窗: 6 months
Improvement of liver fibrosis on MRE (magnetic resonance elastography) \> 2 point
Improvement of quantitative fibrosis
时间窗: 1 year
Improvement of quantitative fibrosis on histology \> 10%
Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State
时间窗: 6 months
Improvement of MELD (Model of End stage Liver Disease) score or Child Pugh State by at least 2 points
Improvement of Fibrosis Staging (Ishak)
时间窗: 3 months
Improvement of Fibrosis Staging (Ishak) \> 1 point
次要结局
- Overall Survival and Improvement(1 year)
- Improvement of Hepatic Venous Pressure(3 months)
- Incidence of clinical decompensation(1 year)
- Overall Improvement of Patient Reported outcome(6 months)
- Overall Improvement of MELD score(1 year)
- Overall Improvement in Liver Function Tests(1 year)