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

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.

Study Overview

• Status: Unknown
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Oseltamivir; Drug: hormones; Device: oxygen therapy; Procedure: mesenchymal stem cells

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Fuzhou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of oxygenation index (PaO2/FiO2) ,blood gas test	Improvement of pulmonary function	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of TNF-α levels, IL-10 levels	Cytokines level	1,3,6,12months
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
Changes of oxygenation index (PaO2/FiO2) ,blood gas test	Improvement of pulmonary function	1,3,6months
Changes of c-reactive protein and calcitonin	Infection biomarkers	1,3,6,12months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: March 25, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (ACTUAL): May 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 1, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Oseltamivir
• Other Study ID Numbers: MSC-CoViD-2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No