Mesenchymal Stem Cells Therapy in Patients With COVID-19 Pneumonia

Study Overview
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Brief Summary
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Due to the cytokine storm that develops as a result of Coronavirus Disease 2019 (COVID-19) infection, some patients hospitalization to intensive care cause of pneumonia, Acute Respiratory Distress Syndrome (ARDS) and multiple organ failure. Mortality is higher in treatment-resistant cases. Purpose of this study: Providing immune modulation by Stem Cell Transplantation and reducing the damage caused by cytokine storm to tissues and organs, Correcting immunosuppression and fight against COVID-19 virus by editing B and T cells, It is to accelerate healing in organ damage by increasing growth factors through mesenchymal stem cells. Primary outcome: Improvement of clinical symptoms, reduction of cytokine storm Secondary outcome: Recovery of patients; from mechanical ventilation

Detailed Description
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Study design and participants This study was a single-center open-label, randomized trial conducted at an Education and Training Hospital, Istanbul from May to July, 2020, and it was performed according to the Declaration of Helsinki and approved by the Ethics Committee and health ministry (No:2020.05.20). Written informed consent was obtained from all patients or their representatives when data were collected prospectively. Age, gender, mortality status, APACHE II score, number of days in ICU, procalcitonin and C-reactive protein values, leukocyte values, comorbid diseases, The cluster of differentiations 4 and 8 (CD4 and CD8), interleukin -2, interleukin -6, Tumor necrosis factor-alpha-beta levels will be recorded. Clinical results, changes in inflammatory and immune function levels, and side effects will be recorded. The patient's lung function and symptoms will be recorded after Mesenchymal Stem Cell transplantation. After treatment, lymphocyte, C-reactive protein, Tumor Necrosis alpha-beta levels , interleukin-6 levels will be recorded. Patients were divided into 3 groups: group: Intubated without comorbidity (n:7) group: Intubated with comorbidity (n:7) group: No intubated (n:7) Dosage of Mesenchymal stem cells: 1 million cell/kg iv--------------------------------------------------day 0 1 million cell/kg iv -------------------------------------------------day 2 1 million cell/kg iv -------------------------------------------------day 4

Official Title
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A 8-Week Trial of Mesenchymal Stem Cells Therapy in Patients With COVID-19 Pneumonia

Conditions
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Coronavirus Disease 2019 (COVID-19) Pneumonia

Intervention / Treatment
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* Other: Mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-90 male or female laboratory approve of RT-PCR (real-time reverse transcription polymerase chain reaction) with COVID-19 infection pneumonia assessed by chest radiography or computed tomography In accordance with any of the following: 1)Respiratory rate ≥ 30 times / min 2) oxygen saturation ≤ 93% 3) arterial pressure of oxygen/the fraction of inspired oxygen≤ 300mmHg, 4) pulmonary imaging of focus within 24-48 hours > 50% progression patients who remain unresponsive to medications administered according to Ministry of health guidelines Patients who receiving invasive or non-invasive mechanical ventilation therapy in intensive care Exclusion Criteria: Pregnancy Any kind of cancer, severe liver disease Failure to provide informed consent or comply with test requirements Known allergy or hypersensitivity to MSCs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Coronavirus Disease 2019 (COVID-19) patients with pneumonia 1.group: Intubated without comorbidity, 2.group: Intubated with comorbidity, 3.group: No intubated
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Intubated without comorbidity | Other: Mesenchymal stem cells<br>* Intravenous infusion of Mesenchymal stem cells<br>|
| Active Comparator: Group 2<br>Intubated with comorbidity | Other: Mesenchymal stem cells<br>* Intravenous infusion of Mesenchymal stem cells<br>|
| Active Comparator: Group 3<br>No intubated | Other: Mesenchymal stem cells<br>* Intravenous infusion of Mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of clinical symptoms as respiratory distress or need for oxygen support | Recovery of patient from mechanical and oxygen support | 3 months | 
| Change of cytokine storm parameters | respiratory rates < 30 times /min | 3 months | 
| Change of pulmonary functions | Oxygen saturation > 93% and pulmonary imaging of focus within 24-48 hours > 50% progression | 3 months | 
| Change of clinical symptoms | arterial pressure of oxygen/the fraction of inspired oxygen>300mmHg | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cells, COVID-19, Pneumonia