Safety and Efficacy Study of Allogeneic Human Menstrual Blood Stem Cells Secretome to Treat Severe Covid-19 Patients, Clinical Trial Phase I&II
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Time to clinical improvement
研究概览
简要总结
In this randomized controlled trial (RCT), severe cases of COVID-19 infection will be treated with secretome of menstrual blood stem cells. The improvement in the clinical, laboratory and radiological manifestations will be evaluated in treated patients compared with the control group.
详细描述
The devastating effect of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) infection is caused by a robust cytokine storm that leads to lung tissue damage. Several studies have found that the severity of the disease is correlated with the release of excessive proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This finding was confirmed by the high level of plasma cytokines found in the most severe COVID-19 patients associated with extensive lung damage. As a result, it is essential to find an effective treatment option to control the devastating cytokine storm of COVID-19 and regenerate the damaged lung. Although mesenchymal stem cells are a powerful tool for clinical applications, they have limits in terms of administration, safety, and variability of therapeutic response. It is interesting to note that the MSC secretome composed of cytokines, chemokines, growth factors, proteins, and extracellular vesicles could be a valid alternative to their use. It is not only easier to preserve, transfer and produce the secretome, but also safer to administer.
Previous studies reported that the hypoxic condition of MSCs could enhance the release of their active soluble molecules known as Secretome-MSCs (S-MSCs), such as IL-10 and TGF-β that useful in alleviating inflammation. Moreover, they could also increase the expression of growth factors such as VEGF and PDGF that accelerate lung injury improvement. These active molecules could potentially serve as a biological therapeutic agent for treating the severe SARS-CoV-2 infection. According to recent studies, we successfully isolated the S-MSCs from their culture medium using tangential flow filtration (TFF) strategy with several molecular weight cut-off category. This study investigated the clinical outcomes of severe COVID-19 patients with several comorbidities treated with S-MSCs in Indonesia.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Assessments regarding clinical recovery will be conducted by the outcomes assessors blind to treatment allocation. Due to the nature of the intervention, staff cannot be blinded to allocation, but the participants are blind to the group to which they belong. An employee outside the research team will feed data into the computer in separate datasheets so that the outcomes assessors can analyses data without having access to information about the allocation.
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients whose clinical and laboratory test results have a positive diagnosis of Covid-
- •Patients who are willing to participate as subjects in the study by signing the informed content.
- •Diagnosed with severe pneumonia of COVID: respiratory distress, RR >30 times/min; resting oxygen saturation of 90% or less; arterial partial pressure of oxygen / oxygen concentration ≤300mmHg; Pulmonary infiltration more than 50% in 24 to 48 hours
- •SARS-CoV-2 nucleic acid test was positive.
排除标准
- •History of drug reactions or allergies
- •Pneumonia caused by bacteria, Mycoplasma, Chlamydia, Legionella, fungi, or other viruses
- •Airway obstruction due to lung cancer or unknown factors
- •Carcinoid syndrome
- •History of epilepsy and long-term use of anticonvulsant drugs during the last 3 years
- •History of long-term use of immunosuppressive drugs
- •History of chronic respiratory illness that requires long-term oxygen therapy
- •The patient is on blood or peritoneal dialysis
- •Creatinine clearance <15 ml / min
- •Moderate to severe liver disease (Child-Pugh score> 12)
- •History of deep vein thrombosis (DVT) or pulmonary embolism over the past 3 years
- •Being under ECMO or high-frequency oscillatory ventilation support
- •Diagnostic of HIV, hepatitis B, and syphilis
- •Pregnant or lactating women
- •Lack of consciousness and inability to provide informed consent by the patient
结局指标
主要结局
Time to clinical improvement
时间窗: Day 0 - 28
Days from administration of the Investigational Product for improvement
Adverse reactions incidence
时间窗: Day 0 - 28
The proportion of participants with treatment-related Adverse Event as assessed by CTCAE v5.0.
次要结局
- Immunological changes on CD4+ T and CD8+ T(Days 0, 5, 10, 14, and 28)
- Assessment of serum D-dimer (microgr/ml) levels(Days 0, 5, 10, 14, and 28)
- Lung Involvement(Day 0 - 28)
- Changes in Inflammatory cytokine IL 6(Days 0, 5, 10, 14, and 28)
- Assessment of serum CRP (mg/L) levels(Days 0, 5, 10, 14, and 28)
- Assessment of serum Ferritin (ng/ml) levels(Days 0, 5, 10, 14, and 28)
- Assessment of serum LDH (U/L) levels(Days 0, 5, 10, 14, and 28)
- Changes in anti-Inflammatory cytokine IL10(Days 0, 5, 10, 14, and 28)