A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia
Condition: Coronavirus
MeSH terms: Pneumonia; Coronavirus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      In December 2019, a novel coronavirus infectious disease characterized by acute respiratory
      impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in
      Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available
      for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with
      mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly
      recommended for severe infected individuals, those with advancing age and co-morbidities such
      as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot
      clinical trial will be performed to explore the safety and efficiency of aerosol inhalation
      of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe
      patients with novel coronavirus pneumonia (NCP).
    

Detailed description: 
      Since December 2019, SARS-CoV-2 infection has become a worldwide urgent public health event,
      especially in China. As of February 13, 2020, over 63,000 cases have been confirmed with over
      10,200 severe cases in mainland of China. There is currently no vaccine or specific antiviral
      treatment existing for SARS-CoV-2 infection. Although symptomatic and supportive care are
      recommended for severe infected individuals, those with advancing age and co-morbidities such
      as diabetes and heart disease remain to be at high risk for adverse outcomes, with mortality
      of ~10%. Therefore, it is urgent to find a safe and effective therapeutic approach to
      patients with severe coronavirus disease-19(COVID-19) characterized by an severe acute
      respiratory impairment.

      Experimental studies have demonstrated that mesenchymal stem cells (MSCs) or their exosomes
      (MSCs-Exo) significantly reduced lung inflammation and pathological impairment resulting from
      different types of lung injury. In addition, macrophage phagocytosis, bacterial killing and
      outcome are improved. It is highly likely that MSCs-Exo have the same therapeutic effect on
      inoculation pneumonia as MSCs themselves.

      Although human bone marrow MSCs have been safely administered in patients with ARDS and
      septic shock (phase I/II trials), it seems safer to deliver MSCs-Exo rather than live MSCs.
      The intravenous administration of MSCs may result in aggregating or clumping in the injured
      microcirculation and carries the risk of mutagenicity and oncogenicity, which do not exist by
      treating with nebulized MSCs-Exo. Another advantage of MSCs-Exo over MSCs is the possibility
      of storing them for several weeks/months allowing their safe transportation and delayed
      therapeutic use.

      The purpose of this single-arm design, open label, combined interventional clinical trial,
      therefore, is to explore the safety and efficiency of aerosol inhalation of the exosomes
      derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in the treatment of severe
      patients hospitalized with novel coronavirus pneumonia (NCP).
    

Intervention name(s): MSCs-derived exosomes
Intervention type(s): Biological
Intervention description(s): 5 times aerosol inhalation of MSCs-derived exosomes (2.0*10E8 nano vesicles/3 ml at Day 1, Day 2, Day 3, Day 4, Day 5).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: mesenchymal stem cells; exosome; nebulization; SARS-CoV-2; novel coronavirus pneumonia