NCT04366063

Mesenchymal Stem Cell Therapy for SARS-CoV-2-related Acute Respiratory Distress Syndrome

Mesenchymal Stem Cell Therapy for Acute Respiratory Distress Syndrome in Coronavirus Infection: A Phase 2-3 Clinical Trial

• Status: Unknown
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Royan Institute · Other Government
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Acute Respiratory Distress Syndrome (ARDS) is the major cause of death in the COVID-19 pandemic. In this trial, the safety and efficacy of Mesenchymal Stem Cells (MSC) for the treatment of ARDS in COVID-19 patients will be assessed.

Detailed description

Acute respiratory distress syndrome (ARDS) is the major cause of death in the COVID 19 infection pandemic. It is a devastating clinical condition, caused by an acute and diffuse lung injury that requires management in the intensive care unit. It is caused by uncontrolled inflammation that leads to severe pulmonary alveolar damage and capillary membrane leakage, and progressive respiratory failure. There is no effective treatment for ARDS and the only supportive care strategies are the mainstay of therapy. Mesenchymal stem cells (MSCs) have high regenerative and immunomodulatory capacities. In preclinical research, ARDS, MSCs modulate the inflammatory response, augment tissue repair, enhance pathogen clearance, and reduce the severity of the injury, pulmonary dysfunction, and apoptosis. Moreover, many studies have shown that the anti-inflammatory effects of MSCs can significantly reduce virus (e.g., Influenza)-induced lung injury and mortality in animals. Since 2014 clinical trials are using MSC from variable sources \[bone marrow (BM), fat, and umbilical cord (UC)\] in the treatment of ARDS. Some of the clinical trials are ongoing and the final reports are not reported. In all final reports, the safety of the application of MSC has been documented and most of them implied improvement in mortality and decrease of morbidity. Moreover, experimental studies have demonstrated that MSCs or their extracellular vesicles (MSCs-EVs) significantly reduced lung inflammation and pathological impairment resulting from different types of lung injury. Also, macrophage phagocytosis, bacterial killing, and the outcome are improved. It is highly likely that MSCs-EVs have the same therapeutic effect on inoculation pneumonia as MSCs themselves. Critically ill coronavirus documented cases suspicious to ARDS (mild or moderate) will be enrolled in the study. Our previous experiment (IRCT20200217046526N1) showed the safety of 3 injections of MSCs in patients with COVID-19. This multi-center trial will recruit 60 patients. All patients in all groups will receive conventional therapy for virus treatment and supportive care for ARDS. The patients allocated randomly to three groups: Control (n=20). Patients will conventional therapy for virus treatment and supportive care for ARDS will be used as control. Intervention Group1 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 intravenously. Intervention Group 2 (n=20). Patients will receive two doses of MSCs 100×10e6 (±10%), at Day 0 and Day 2 plus two doses of extracellular vesicles (EVs) on Day 4 and Day 6 intravenously. The clinical symptoms, pulmonary imaging, side effects, 28-days mortality inflammatory factors, etc. will be evaluated during the 28 days follow up.

Conditions

• Covid-19

Interventions

Type	Name	Description
BIOLOGICAL	Cell therapy protocol 1	Cell therapy protocol 1(n=20). Patients will receive two doses of MSCs 100×10e6 (±10%) at Day 0 and Day 2 plus Conventional treatment.
BIOLOGICAL	Cell therapy protocol 2	Patients will receive two doses of MSCs 100×10e6 (±10%)at Day 0 and Day 2, intravenously plus two doses of EVs at Day 4 and Day 6 plus conventional treatment.

Timeline

• Start date: 2020-04-05
• Primary completion: 2020-06-06
• Completion: 2020-12-10
• First posted: 2020-04-28
• Last updated: 2020-04-30

Locations

1 site across 1 country: Iran