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

• ClinicalTrials.gov Identifier: NCT04371601
• Recruitment Status: Unknown
• First Posted: May 1, 2020
• Last Update Posted: May 1, 2020
• Sponsor: Fuzhou General Hospital
• Information provided by (Responsible Party): Fuzhou General Hospital

Tracking Information

• First Submitted Date: March 25, 2020
• First Posted Date: May 1, 2020
• Last Update Posted Date: May 1, 2020
• Actual Study Start Date: March 1, 2020
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2020)

Changes of oxygenation index (PaO2/FiO2) ,blood gas test [ Time Frame: 12 months ]

Improvement of pulmonary function

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 30, 2020)

• Detection of TNF-α levels, IL-10 levels [ Time Frame: 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). [ Time Frame: 1,3,6,12months ]
  Immunological status
• Changes of oxygenation index (PaO2/FiO2) ,blood gas test [ Time Frame: 1,3,6months ]
  Improvement of pulmonary function
• Changes of c-reactive protein and calcitonin [ Time Frame: 1,3,6,12months ]
  Infection biomarkers

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

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.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: COVID-19 Pneumonia

Intervention

• 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

Study Arms

• Active Comparator: Control group
  conventional symptomatic treatments such as antiviral (oseltamivir), hormones, oxygen therapy, mechanical ventilation and other supportive therapies
  Interventions:

  • Drug: Oseltamivir
  • Drug: hormones
  • Device: oxygen therapy
• 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
  Interventions:

  • Drug: Oseltamivir
  • Drug: hormones
  • Device: oxygen therapy
  • Procedure: mesenchymal stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: April 30, 2020): 60
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04371601
• Other Study ID Numbers: MSC-CoViD-2020
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fuzhou General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Fuzhou General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Fuzhou General Hospital
• Verification Date: March 2020