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

Sponsor

Fuzhou General Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04371601

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Pneumonia	Drug: Oseltamivir Drug: hormones Device: oxygen therapy Procedure: mesenchymal stem cells	Early Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control group conventional symptomatic treatments such as antiviral (oseltamivir), hormones, oxygen therapy, mechanical ventilation and other supportive therapies	Drug: Oseltamivir Oseltamivir capsules Drug: hormones a moderate amount of hormone Device: oxygen therapy oxygen therapy,mechanical ventilation and other supportive therapies
Experimental: 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	Drug: Oseltamivir Oseltamivir capsules Drug: hormones a moderate amount of hormone Device: oxygen therapy oxygen therapy,mechanical ventilation and other supportive therapies Procedure: mesenchymal stem cells mesenchymal stem cells

Arm

Intervention/Treatment

Active Comparator: Control group

conventional symptomatic treatments such as antiviral (oseltamivir), hormones, oxygen therapy, mechanical ventilation and other supportive therapies

Drug: Oseltamivir

Oseltamivir capsules

Drug: hormones

a moderate amount of hormone

Device: oxygen therapy

oxygen therapy,mechanical ventilation and other supportive therapies

Experimental: 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

Drug: Oseltamivir

Oseltamivir capsules

Drug: hormones

a moderate amount of hormone

Device: oxygen therapy

oxygen therapy,mechanical ventilation and other supportive therapies

Procedure: mesenchymal stem cells

mesenchymal stem cells

Outcome Measures

Primary Outcome Measures

Changes of oxygenation index (PaO2/FiO2) ,blood gas test [12 months]
Improvement of pulmonary function

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fuzhou General Hospital	Fuzhou	Fujian	China	350025

Sponsors and Collaborators

Fuzhou General Hospital

Investigators

Study Chair: Jianming Tan Tan, M.D and Ph.D, Fuzhou General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Fuzhou General Hospital

ClinicalTrials.gov Identifier:

NCT04371601

Other Study ID Numbers:

MSC-CoViD-2020

First Posted:

May 1, 2020

Last Update Posted:

May 1, 2020

Last Verified:

Mar 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of May 1, 2020