Clinical trial NCT04371601: Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019
Official title: Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: COVID-19 Pneumonia
Lead sponsor: Fuzhou General Hospital
Sponsor class: OTHER
First posted: 2020-05-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Control group: conventional symptomatic treatments such as antiviral (oseltamivir), hormones, oxygen therapy, mechanical ventilation and other supportive therapies; Experimental group: On the basis of the above-mentioned conventional symptomatic treatment and supportive therapy, umbilical cord mesenchymal stem cells were given at 106 / Kg body weight / time, once every 4 days for a total of 4 times. Peripheral intravenous infusion was given within 3 days of first admission.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test
timeFrame: 12 months
Secondary outcomes:
measure: Detection of TNF-α levels, IL-10 levels
timeFrame: 1,3,6,12months
measure: Detection of immune cells that secret cytokines, including CXCR3+, CD4+, CD8+, NK+ cells, and regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells).
timeFrame: 1,3,6,12months
measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test
timeFrame: 1,3,6months
measure: Changes of c-reactive protein and calcitonin
timeFrame: 1,3,6,12months
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fuzhou General Hospital
state: Fujian
Study officials:
affiliation: Fuzhou General Hospital
name: Jianming Tan Tan, M.D and Ph.D
role: STUDY_CHAIR
References: