Mesenchymal Stem Cells for the Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID-19. Pilot Study
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Clinical Respiratory Changes: Respiratory rate per minute
Study Overview
Brief Summary
Acute Respiratory Distress Syndrome (ARDS) is the main cause of death from COVID-19. One of the main mechanisms for ARDS is the violent storm of cytokines and chemokines, which cause uncontrolled fatal systemic inflammation by the immune system on the body, with additional multiple organ failure. Mortality in cases of severe ARDS caused by COVID 19 varies significantly between 50 and 90%, basically depending on the age of the patient and the presence of comorbidities.
The plasticity of Mesenchymal Stem Cells (MSC) regulates inflammation and immunity. MSC can promote and inhibit an immune response, depending on the dynamics of inflammation and depending on the activation force of the immune system, the types of inflammatory cytokines present, and the effects of immunosuppressants. Essentially, the state of inflammation determines the immunoregulatory fate of MSC. Thus, IV application of AMSCa has been shown to control the inflammatory response in various diseases, such as the graft-versus-host reaction and the ARDS caused by H5NI.
The objective of this study is to describe the clinical changes secondary to IV administration of MSC allogenic, in patients with bilateral COVID-19 pneumonia complicated by severe ARDS, with the evaluation of the PaO2 / FiO2 ratio, heart and respiratory rates, and the fever curve.
Five patients, of either sex, over 18 years of age, with bilateral pneumonia caused by COVID-19 and severe SIRA that has not improved with the standard management measures used at that time in the care center, will be included in the study. This treatment will be administered after discussing it with the relatives that it is a procedure considered as rescue and will be carried out with informed consent. 1x10(6) xKg will be applied IV.
The follow-up of the patient will be for three weeks. PaO2 / FiO2 data, fever, inflammatory markers and immunity will be evaluated. The results will be compared with the historical controls attended at INCMNSZ.
Detailed Description
Acute Respiratory Distress Syndrome (ARDS) is the main cause of death from COVID-19. One of the main mechanisms for ARDS is the storm of cytokines and chemokines, which cause uncontrolled fatal systemic inflammation. The SARS-CoV-2 virus infects cells that express the angiotensin II converting enzyme receptor (ACE2). This receptor is widely distributed on the surface of type II alveolar cells (AT2) and on the capillary endothelium. This is why the cytokine storm will trigger a violent attack by the immune system on the body, cause ARDS and multiple organ failure, and can ultimately lead to death. Mortality in cases of severe SIRA caused by COVID 19 varies significantly between 50 and 90%, basically depending on the age of the patient and the presence of comorbidities.
The plasticity of Mesenchymal Stem Cell (MSC) regulates inflammation and immunity. MSC can promote and inhibit an immune response, depending on the dynamics of inflammation and depending on the activation force of the immune system, the types of inflammatory cytokines present, and the effects of immunosuppressants. Essentially, the state of inflammation determines the immunoregulatory fate of MSC. Thus, IV application of MSC has been shown to control the inflammatory response in various diseases, such as the graft-versus-host reaction and the ARDS caused by H5NI.
MSC are negative for ACE2, therefore they have been used to decrease the cytokine storm present in COVID-19.
Two recent studies in China have used human allogeneic MSC to treat COVID-19 pneumonia. Both studies reveal a marked reversal of symptoms, even in critically serious cases. Lung function improved two days after MSC application and 10 days later they were discharged. Lymphocytes increased, PCR decreased, and cytokine-producing immune cells disappeared within 3 to 6 days. Regulatory immune cells increased. TNF alpha factor decreased and IL10 increased.
Taking into account the previous concepts together with the current global pandemic, and the high mortality existing among patients with bilateral pneumonia caused by COVID-19 and severe ARDS, the investigators propose intravenous infusion of mesenchymal stem cells from bank laboratory, with the purpose partially proven to decrease the systemic inflammatory process, offering it as a salvage treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Bilateral pneumonia due to COVID-19
- •With SARS-Cov2 PCR RNA detection test, positive
- •Severe ARDS
- •PaO2/FiO2 <150
- •Leukocytes < 800
- •Chest TAC with pneumonia bilateral
- •persistant fever
- •increase 50% D-Dimer, respect to basal value
- •Ferritin > 1000
- •SOFA < 11
- •Medical treatment during 48 hr according to de Institutional Medical center
- •With knowledge of the patient and / or his relatives responsible that it is a rescue treatment, in experimental phase.
Exclusion Criteria
- •Pneumonia or ARDS caused by COVID-19, mild and moderate.
- •More than three organic failures
- •Expectations of survival less than 48 hr in the opinion of the treating service
- •Pneumonia or SIRA not caused by COVID-19
- •Advance will of the patient to refuse rescue or experimental treatment.
Outcomes
Primary Outcomes
Clinical Respiratory Changes: Respiratory rate per minute
Time Frame: Three weeks
To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the respiratory rate per minute.
Functional Respiratory changes: PaO2 / FiO2 ratio
Time Frame: Three weeks
To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the PaO2 / FiO2 ratio.
Clinical cardiac changes: Heart rate per minute
Time Frame: Three weeks
To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the heart rate per minute.
Changes in body temperature
Time Frame: Three weeks
To describe the clinical changes secondary to IV administration of AMSCa, in patients with bilateral COVID-19 pneumonia complicated by severe SIRA, with the evaluation of the fever curve in degrees centigrade.
Secondary Outcomes
- General biochemical changes on pocalcitonin(Three weeks)
- Changes on Inflammatory cytokine IL10(Three weeks)
- General biochemical changes in Leukocytes(Three weeks)
- General biochemical changes on platelets(Three weeks)
- Cahnges on Inflammatory cytokine TNFa(Three weeks)
- Changes on Inflammatory cytokine IL6(Three weeks)
- RNA detection by SARS-Cov2 PCR(Three weeks)
- General biochemical changes on fibrinogen(Three weeks)
- General biochemical changes on D-dimer(Three weeks)
- Changes on Inflammatory cytokine IL1(Three weeks)
- Changes on Inflammatory cytokine IL 17(Three weeks)
- Changes on VEGF(Three weeks)
- Radiological Changes(Three weeks)
- Immunological changes on T cell(Three weeks)
- Immunological changes on CD4+ T(Three weeks)
- Immunological changes on CD8+ T(Three weeks)
- Adverse events(Three weeks)
- General biochemical changes on lymphocytes(Three weeks)
- General biochemical changes on ferritin(Three weeks)
- Changes on inflammatory C-reactive protein(Three weeks)
- Immunological changes on Dendritic cells(Three weeks)
- Immunological changes on NK cell(Three weeks)
Investigators
Martín Iglesias
Plastic surgeon
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran