Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Pneumonia.
Condition: Covid19; SARS-CoV-2 PNEUMONIA; COVID-19
MeSH terms: COVID-19; Pneumonia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Coronavirus is an acute viral disease with prevailing upper respiratory tract infections
      caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family.
      Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the
      infection progresses, the infiltration increases, and the affected areas increases. Excessive
      and uncontrolled immune system response with rapidly developing fatal cytokine storm plays
      the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to
      SARS-CoV-2 infection.

      According to available data, exosomes can regulate inflammation and regenerative processes
      due to the change in the concentration of anti-inflammatory cytokines and switch the immune
      cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to
      the lung tissue and stimulate the regenerative processes.

      This protocol has been developed based on the literature, information about the ongoing tests
      NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating
      Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With
      COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating
      microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and
      pharmaceutical products to stimulate regenerative processes and slow down aging.
    

Detailed description: 
      COVID-19 is an infectious disease caused by the most recently discovered coronavirus. This
      new virus and disease were unknown before the outbreak began in Wuhan, China, in December
      2019. COVID-19 is now a pandemic affecting many countries worldwide. Globally, as of 1:09 pm
      CEST, 27 July 2020, there have been 16 096 741 confirmed cases of COVID-19, including 646 384
      deaths, reported to WHO.

      The main and rapidly achievable target of SARS-CoV-2 is lung type II alveolar cells (AT2),
      which determines the development of diffuse alveolar damage. In the pathogenesis of ARDS due
      to COVID-19, the main role is played by an over-response of the immune system with rapidly
      developing severe life-threatening cytokine release syndrome (cytokine storm). Cytokine
      release syndrome threatens the emergence and progression of ARDS. The key components of the
      pathogenesis of ARDS also include disruption of cell cytotoxicity mechanisms, excessive
      activation of cytotoxic lymphocytes and macrophages with a massive release of proinflammatory
      cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic colony-stimulating factor,
      monocytic chemoattractive protein 1), and inflammatory markers (CRP, serum ferritin),
      infiltration of internal organs and tissues by activated T-lymphocytes and macrophages,
      resulting in a hyperinflammatory reaction. Such severe lesions can lead to death or severe
      lung damage, including long rehabilitation after discharge.

      Experimental studies have demonstrated that mesenchymal stem cells (MSCs) may significantly
      reduce lung inflammation and pathological impairment resulting from different types of lung
      injury. Many researchers connect the anti-inflammatory effect of MSC with their secretome
      which includes MSC derived exosomes. It is highly likely that MSC exosomes have the same
      therapeutic effect on inoculation pneumonia as MSCs themselves. Moreover, exosomes show a
      strong effect of regenerative stimulation on different wounds so the regenerative effect can
      be extended on patients with COVID-19 pneumonia.

      The purpose of this protocol is to explore the safety and efficiency of aerosol inhalation of
      the exosomes in the treatment of severe patients hospitalized with novel coronavirus
      pneumonia (NCP).
    

Intervention name(s): EXO 1 inhalation; EXO 2 inhalation; Placebo inhalation
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the first type.; Twice a day during 10 days inhalation of 3 ml special solution contained 0.5-2x10^10 of nanoparticles (exosomes) of the second type.; Twice a day during 10 days inhalation of 3 ml special solution free of nanoparticles (exosomes).
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The trial has three groups, each with 10 subjects (n=30). All eligible study subjects will be randomized, double-blinded, to either the two treatment groups or placebo group.
Masking: Double (Participant, Care Provider)
Primary purpose: Other
Keywords: Covid-19; SARS-CoV-2; exosomes; MSC