Safety and Efficacy of Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells in Severe Patients With Coronavirus Disease 2019 (COVID-19): A Phase 1/2 Randomized Controlled Trial
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
- Changes of oxygenation index (PaO2/FiO2)
研究概览
简要总结
Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.
详细描述
COVID-19 has become a urgent and serious public health event that threatens human life and health globally. No specific pharmacological treatments are available to date for COVID-19.Patients contracting the severe form of the disease constitute approximately 15% of the cases which is characterized by extensive acute inflammation. In these severe cases, there will be rapid respiratory system failure.
MSCs have been employed extensively in cell therapy, which includes a plethora of preclinical research investigations as well as a significant number of clinical trials. Safety and efficacy have been shown in many clinical trials. Previous studies have shown that MSCs could significantly reduce inflammatory cell infiltration in lung tissue, reduce inflammation in lung tissue, and significantly improve lung The structure and function of tissues protect lung tissue from damage.The mechanisms underlying the improvements after MSC infusion in COVID-19 patients also appeared to be the robust antiinflammatory activity of MSCs. Recent studies also showed that intravenous MSC infusion could reduce the overactivation of the immune system and support repair by modulating the lung microenvironment after SARS-CoV-2 infection. MSC therapy inhibiting the overactivation of the immune system and promoting endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection.
The purpose of this study is to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients With COVID-19.The respiratory function, pulmonary inflammation, clinical symptoms, pulmonary imaging, side effects, immunological characteristics will be evaluated.
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 (Participant)
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 and able to provide written informed consent prior to performing study procedures
- •Age ≥18 years, and ≤75 years;
- •A confirmed case of Covid-
- •The criteria are as follows:
- •Clinically diagnosed or suspected cases with one of the following etiological evidence: 1) SARS-CoV-2 nucleic acid is positive in respiratory or blood samples detected by RT-PCR; 2) virus sequence detected in respiratory or blood samples shares high homology with the known sequence of SARS-CoV-
- •Clinical classification is severe case: Meet any of the following:
- •Increased respiratory rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; 2) Peripheral capillary oxygen saturation (SpO2) ≤93% at rest ; 3)Partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa).
排除标准
- •Other types of viral pneumonia, or bacterial pneumonia.
- •The clinical classification is mild, moderate or critical;
- •Patients with malignant blood or solid tumor.
- •Pregnant or lactating women;
- •There are other situations or diseases that the investigator think are not suitable to participate in this clinical study or may be increased risk of the subject.
- •Patients with serious social and mental disability, inability/restriction of legal capacity;
- •Refusal to sign informed consent;
- •Patients with severe liver disease (eg Child Pugh score ≥ C, AST> 5 times upper limit of normal );
- •Patients with severe renal insufficiency (estimated glomerular filtration rate ≤30mL / min / 1.73m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis.
结局指标
主要结局
Changes of oxygenation index (PaO2/FiO2)
时间窗: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
Evaluation of pneumonia improvement
Side effects in the BM-MSCs treatment group
时间窗: Baseline through 6 months
Proportion of participants with treatment-related adverse events
次要结局
- CT Scan(At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.)
- Rate of mortality within 28-days(From baseline to day 28)
- Changes of C-reactive protein(At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.)
- Clinical outcome(At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.)
- Hospital stay(Baseline through 6 months)
- Changes in viral load(At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.)
- Changes of CD4+, CD8+ cells count and concentration of cytokines(At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.)
研究者
ShiYue Li
Professor
Guangzhou Institute of Respiratory Disease