Evaluation of the Safety and Efficiency of Mesenchymal Stem Cell Derived Exosomes in patients with ARDS of COVID-19; An interventional randomized double-blind controlled clinical trial: phase I and II

The use of mesenchymal stem cells-derived exosomes that were cultured in an inflammatory niche, can have beneficial effects in preventing or reducing cytokine storms due to the high modulating potential of the immune system, and reduce the complications and mortality of this disease.

A controlled trial with parallel groups, double-blind, randomized, phases 1 and 2 on 72 patients. The random sequence table was used to randomize the blocks.

In the Stem Cell Center for Excellence of Iran University of Medical Sciences, Stem cells will be cultured in DMEM/F12 with 10% serum. The inflammatory niche will be provided with interleukin 1-beta. Ultracentrifugation purifies the extracellular vesicles of the cell culture supernatant. Exosomes are resolved in PBS and after the Quality Control tests will be prescribed at 100 million/kg. The patient, treating physician, and the physician who follow-up are blinded.

Inclusion Criteria: 1- Definitive infection with COVID-19 confirmed by PCR 2- Acute respiratory distress Syndrome of moderate to severe type (PaO2/ FiO2 <200mmHg) 3- Age between 18 to 65 years from both Sexes 4- No Participation in another clinical trial during this study 5- Written informed consent Exclusion Criteria: 1- Malignant diseases 2- Pregnancy 3- Symptoms or history of liver or kidney failure 4- History of lung surgery or Lung transplantation 5- Having an autoimmune disease or Metabolic disorders 6- Severe trauma occurred within 14 days 7- Who are undergoing hemodialysis or peritoneal dialysis

1- Intravenous injection of 500ml normal saline contains umbilical cord mesenchymal stem cell-derived Exosomes 2- Intravenous injection of normal saline

Adverse reaction and severe adverse reaction; Time to clinical improvement

In this study, the Stratified Block Randomization method is used to randomize patients in the intervention and control groups. Because patients with different intensities are in the study, classification is based on the type of need or lack of need for respiratory support. Patients who need respiratory support in the form of mechanical ventilation are classified in group A and patients who need nasal cannula or do not need respiratory support are classified in group B. The blocks used are of sizes 2, 4, and 8, and based on the probable number of people participating in the study with any severity of the disease, blocks with the appropriate volume are used to generate random codes. In order to place patients in control and intervention groups, a random sequence table is created with the help of SAS 9.1 software. Each patient is assigned a completely random sequence number, and random numbers are placed in envelopes (exactly the same, completely closed, with no transparency to view the contents of the envelope). Patients choose one of the envelopes as they wish. Envelopes are kept by a researcher, who does not participate in the study and is not aware of the type of study until the data is collected. Only in case of severe complications, the researcher will be notified through the main project partner to open the relevant envelope.

In this study, the participant in the intervention, his / her clinical caregiver, trial researcher, and outcome assessor did not know that they were prescribing the intervention drug or placebo.

Some of the data is potentially shareable after blinding persons

Access period starts 6 months after the results are published

All people

Hospitals for medical purposes and researchers for faster development of projects

The person in charge of the scientific support of the clinical trial Stem Cell and Reconstructive Medicine Research Center, Iran University of Medical Sciences Shahid Motahari Hospital cell.therapy@yahoo.com

A written request stating the reasons for the need for the data