Efficacy and Safety of EXOSOME-MSC (Mesenchymal Stem Cell-Derived Exosomes) Therapy to Reduce Hyper-inflammation In Moderate COVID-19 (2019- New Corona Virus Disease) Patients
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Time to clinical improvement (days)
研究概览
简要总结
In COVID-19 infection caused by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dysregulation of the immune system response that causes cytokine storm syndrome. SARS-CoV-2 works like a hijacker (hackers), sabotaging communication between cells so that the immune system, like T-cells, kills not only infected cells but also healthy cells. This dysregulation results in hyper-inflammation which cause damage to organs, not just the lungs. This is the cause of the high mortality rate in COVID-19 patients.
Exosomes are vesicles with a size of 30-100 nanometers originating from within cells that function to communicate with other cells. Exosomes are transport containers that contain bioactive cargo: such as proteins, genetic material, and various other molecules. These containers move from cells of origin, flowing through blood vessels or other body fluids to target cells. Exosomes penetrate the cell membrane and act on various organelles within the target cell.
All cell types can produce exosomes. What differentiates them is the cargo they contain. The exosome produced by mesenchymal stem cells (MSCs) contains bioactive cargo derived from mesenchymal stem cells, such as anti-inflammatory cytokines, growth factors, messengerRNA (mRNA) and microRNA (miRNA). The target cells are immune system cells, infected cells and progenitor cells from infected organs. On target immune cells, the anti-inflammatory cytokines work as immunomodulators to relieve hyper-inflammation. In infected cells, the miRNAs work to prevent viral replication by inhibiting the expression of SARS-CoV-2 virus RNA (viral mRNA silencing and degrading). In lung progenitor cells and other infected organs, the growth factors work to stimulate protein synthesis processes that function for organ regeneration.
This study is a multi-center, double-blind, randomized controlled trial (RCT) clinical trial with two arms: one intervention arm, and one control arm. The EXOSOME-MSC will be tested as adjuvant, on top of standard COVID-19 drugs. It will be injected to participants via intravenous route twice, in day-1 and day-7 of 14 days of study participation.
详细描述
The current study is a multi-center, double arm, adjuvant, randomized control trial (RCT), double-blind clinical trial, to analyze the differences in the usefulness and safety of Exosome-MSC intravenous injection therapy in moderate-grade COVID-19 patients with hyper-inflammation (Evans S.R, 2010).
This study used 2 groups (double arm) of study participants:
Treatment Group (Intervention Arm): received treatment in the form of standard therapy and injection of Exosomes-MSC.
Control Group (Control Arm): received treatment in the form of standard therapy and injection placebo.
The time interval for the implementation of the study protocol was 14 days. For each group (Treatment and Control) the minimum target number of participating patients and according to the inclusion criteria in this study were 30 people. The minimum total number of participants with 2 groups (Treatment and Control) is 60 people. (Rohrig B., 2010)
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
- Triple (Participant, Care Provider, Investigator)
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
- •Diagnosed with COVID-19 pneumonia confirmed by RT-PCR examination. Samples were obtained from nasopharyngeal swabs in patients with moderate
- •There is evidence of changes in chest X-ray with a picture of COVID-19 pneumonia and/or CT-Scan of the thorax with a ground glass opacity picture
- •Willing to participate in the study and sign the informed consent by the subject or family members.
排除标准
- •Diagnosed with mild COVID-19 pneumonia
- •Pregnant woman or positive pregnancy test
- •The subject is participating in another clinical trial.
- •Have a history of anaphylactic reactions, angioedema, or allergic reactions to antibiotics (penicillin and its derivatives) or other drugs.
- •Have an autoimmune disease
- •Have a history of malignancy
- •Undergoing hemodialysis or peritoneal dialysis
- •Recuring COVID-19 sufferers
研究组 & 干预措施
Intervention group
Group participants who receive injection of EXOSOME-MSC as adjuvant
干预措施: Exosome-MSC Intravenous injection (Drug)
Intervention group
Group participants who receive injection of EXOSOME-MSC as adjuvant
干预措施: COVID-19 Standard Treatment (Drug)
Control group
Group participants who receive injection of Placebo (NaCL) as adjuvant
干预措施: Placebo Intravenous Injection (Drug)
Control group
Group participants who receive injection of Placebo (NaCL) as adjuvant
干预措施: COVID-19 Standard Treatment (Drug)
结局指标
主要结局
Time to clinical improvement (days)
时间窗: 14 days
Clinical improvement is fulfilled with score 1-3 of the scale 1. No hospitalization and no restrictions activity 2. Not hospitalized, with activity restrictions, oxygen requirements at home, or both 3. Hospitalized, does not require oxygen additional and no longer need maintenance ongoing medical treatment (used if hospitalization is extended for infection control or other reasons nonmedical) 4. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (related to COVID-19 or other medical conditions) 5. hospitalized, requires supplemental oxygen 6. hospitalized, requiring noninvasive ventilation or use high flow oxygen device; 7. hospitalized, receiving mechanical ventilation invasive or extracorporeal membrane oxygenation (ECMO); 8. deaths.
次要结局
- Decrease in LDH level(14 days)
- Increase in Lymphocytes counts(14 days)
- Decrease in D-dimer(14 days)
- Decrease in Ferritin concentration(14 days)
- Decrease in C-reactive protein(14 days)
- Adverse events(14 days)
研究者
Bambang Darwono
Senior Clinical Consultant
Dermama Bioteknologi Laboratorium