NCT04798716

The Use of Exosomes for the Treatment of Acute Respiratory Distress Syndrome or Novel Coronavirus Pneumonia Caused by COVID-19

Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19 Positive Patients With Acute Respiratory Distress Syndrome and/or Novel Coronavirus Pneumonia

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: AVEM HealthCare · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Novel coronavirus pneumonia (NCP) and acute respiratory distress syndrome (ARDS) are both associated with the prevailing upper respiratory tract infections caused by the RNA-containing SARS-CoV2 virus of the genius Betacoronavirus of the Coronaviridae family. As both the viral infiltration and infection progress, the host immune system response can be one of a rapidly developing fatal cytokine storm. In the ARDS or NCP ensuing progression, the patient often succumbs to the effects of the hyper pro-inflammatory response, hence contributing to the associated increased mortality as a result of the cytokine storm and associated pathogenesis.

Detailed description

In December of 2019, in Wuhan, China, a novel coronavirus outbreak began. Globally this disease referred to as COVID-19, is the result of a novel SARS-CoV2 virus which predominantly targets Type II lung alveolar cells (AT2). The hyper response of the host immune system can rapidly evolve into a life-threatening cytokine-release syndrome or cytokine storm. The cytokine storm can predispose the patient to ARDS and/or NCP., or both. Left unchecked, the ARDS pathogenesis rapidly culminates in disruption of cell cytotoxicity mechanisms, excessive activation of cytotoxic lymphocytes, and a predominance of type I (M1) macrophage; resulting in the massive release of a host of proinflammatory cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic colony-stimulating factor, monocytic chemoattractive protein 1. The result systemically is a rise in surrogate inflammatory markers (C Reactive Protein, serum ferritin), with a corresponding infiltration of internal organs and tissues by activated macrophage, T-lymphocytes and a predominance of cellular apoptosis. The resulting hyperinflammatory pathogenic reaction may result in severe aveolar lesions leading to death, scarring, or severe lung damage, persisting well after discharge. Experimental studies have demonstrated that mesenchymal stem cells (MSCs) and MSC-culutre media (MSC-CM) may significantly reduce the pro-inflammatory bias and associated pathologic impairment resulting. The MSC-CM, known to contain exosomes, has been shown to have an anti-inflammatory effect. Further exosomes associated with the amniotic membrane, long used in the treatment of burn and wounds, have been show to have a regenerative effect. The purpose of this protocol is to explore the safety and efficacy of an intravenous injection of MSC derived exosomes in the treatment of severe patients (moderate to severe Berlin score) with ARDS or NCP.

Conditions

• Covid19
• Novel Coronavirus Pneumonia
• Acute Respiratory Distress Syndrome

Interventions

Type	Name	Description
DRUG	MSC-exosomes delivered intravenously every other day on an escalating dose: (2:4:8)	Escalating dose 2 X 10\^9, 4 X 10\^9, 8 X 10\^9/mL
DRUG	MSC-exosomes delivered intravenously every other day on an escalating dose (8:4:8)	Escalating dose 8 X 10\^9, 4 X 10\^9, 8 X 10\^9 mL
DRUG	MSC-exosomes delivered intravenously every other day (8:8:8)	Dosed 8 X 10\^9, 8 X 10\^9, 8 X 10\^9 mL

Timeline

• Start date: 2023-09-01
• Primary completion: 2024-09-01
• Completion: 2024-12-01
• First posted: 2021-03-15
• Last updated: 2022-03-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study