Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019

COVID-19 Pneumonia Clinical Trial

Official title:

Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04371601
• Other study ID #: MSC-CoViD-2020
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: March 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2020
• Source: Fuzhou General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 has seen numerous patients experiencing severe acute lung injury (ALI), which developed into severe respiratory distress syndrome (ARDS). The mortality was as high as 20% -40%. Due to the lack of effective antiviral treatments, supporting treatment is the predominant therapy for COVID-19 pneumonia. Its cure is essentially dependent on the patient's immunity. While the immune system eliminates the virus, numerous inflammatory cytokines are produced and a cytokine storm occurs in severe cases.

Mesenchymal stem cells (MSCs) play an important role in injury repair and immune regulation, showing advantageous prospects in the treatment of COVID-19 pneumonia. MSCs prevent cytokine storms by retarding the TNF-α pathway, alleviate sepsis by modulating macrophages, neutrophils, NK cells, DC cells, T lymphocytes and B lymphocytes. After infused, MSCs aggregate in the lungs, improve the lung microenvironment, protect alveolar epithelia, and improve pulmonary fibrosis and pulmonary function.

Description:

In vitro, Mesenchymal stem cells were revealed to inhibit the secretion of inflammatory cytokines by spleen lymphocytes and up-regulate regulatory T cells, thereby inhibiting the secretion of interferon-γ(IFN-γ) induced by lymphocytes and Tumor Necrosis Factor(TNF) induced by macrophage.

Animal models and preclinical studies have shown that mesenchymal stem cells (MSCs) were implanted into inflammatory lung tissues after infusion, which significantly improved the clinical manifestations and histopathological lesions caused by acute lung injury. Mesenchymal stem cells inhibited the effects of interleukin-1 (IL-1) through regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells) and by antagonizing the expression interleukin-1 receptor (IL1-RA). Mesenchymal stem cells significantly down-regulated pro-inflammatory factors by inhibiting the expression of IL-1, TNF and IFN-γ in lung tissue, and up-regulated anti-inflammatory factor by enhancing the expression of IL -10 and regulatory T cells, respectively, thereby dampening the inflammatory response.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• patients with severe COVID-19 pneumonia

• willing to give informed consent

Exclusion Criteria:

• patients with mild COVID-19 pneumonia

• liver dysfunction

• concomitant with other active infection

• renal dysfunction

• Heart failure >grade 2

• pregnant

• history of COPD

Related Conditions & MeSH terms

• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Oseltamivir
Oseltamivir capsules
• hormones
a moderate amount of hormone

Device:
• oxygen therapy
oxygen therapy,mechanical ventilation and other supportive therapies

Procedure:
• mesenchymal stem cells
mesenchymal stem cells

Locations

Country	Name	City	State
China	Fuzhou General Hospital	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fuzhou General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of oxygenation index (PaO2/FiO2) ,blood gas test	Improvement of pulmonary function	12 months
Secondary	Detection of TNF-a levels, IL-10 levels	Cytokines level	1,3,6,12months
Secondary	Detection of immune cells that secret cytokines, including CXCR3+, CD4+, CD8+, NK+ cells, and regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells).	Immunological status	1,3,6,12months
Secondary	Changes of oxygenation index (PaO2/FiO2) ,blood gas test	Improvement of pulmonary function	1,3,6months
Secondary	Changes of c-reactive protein and calcitonin	Infection biomarkers	1,3,6,12months