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Bone Marrow-Derived Mesenchymal Stem Cell Treatment for Severe Patients With Coronavirus Disease 2019 (COVID-19)

Phase 1
Conditions
Coronavirus Disease 2019 (COVID-19)
Interventions
Biological: Placebo
Biological: BM-MSCs
Registration Number
NCT04346368
Lead Sponsor
Guangzhou Institute of Respiratory Disease
Brief Summary

Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.

Detailed Description

COVID-19 has become a urgent and serious public health event that threatens human life and health globally. No specific pharmacological treatments are available to date for COVID-19.Patients contracting the severe form of the disease constitute approximately 15% of the cases which is characterized by extensive acute inflammation. In these severe cases, there will be rapid respiratory system failure.

MSCs have been employed extensively in cell therapy, which includes a plethora of preclinical research investigations as well as a significant number of clinical trials. Safety and efficacy have been shown in many clinical trials. Previous studies have shown that MSCs could significantly reduce inflammatory cell infiltration in lung tissue, reduce inflammation in lung tissue, and significantly improve lung The structure and function of tissues protect lung tissue from damage.The mechanisms underlying the improvements after MSC infusion in COVID-19 patients also appeared to be the robust antiinflammatory activity of MSCs. Recent studies also showed that intravenous MSC infusion could reduce the overactivation of the immune system and support repair by modulating the lung microenvironment after SARS-CoV-2 infection. MSC therapy inhibiting the overactivation of the immune system and promoting endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection.

The purpose of this study is to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients With COVID-19.The respiratory function, pulmonary inflammation, clinical symptoms, pulmonary imaging, side effects, immunological characteristics will be evaluated.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
20
Inclusion Criteria
  1. Willing and able to provide written informed consent prior to performing study procedures

  2. Age ≥18 years, and ≤75 years;

    A confirmed case of Covid-19. The criteria are as follows:

    Clinically diagnosed or suspected cases with one of the following etiological evidence: 1) SARS-CoV-2 nucleic acid is positive in respiratory or blood samples detected by RT-PCR; 2) virus sequence detected in respiratory or blood samples shares high homology with the known sequence of SARS-CoV-2.

  3. Clinical classification is severe case: Meet any of the following:

  1. Increased respiratory rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; 2) Peripheral capillary oxygen saturation (SpO2) ≤93% at rest ; 3)Partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa).
Exclusion Criteria
  1. Other types of viral pneumonia, or bacterial pneumonia.
  2. The clinical classification is mild, moderate or critical;
  3. Patients with malignant blood or solid tumor.
  4. Pregnant or lactating women;
  5. There are other situations or diseases that the investigator think are not suitable to participate in this clinical study or may be increased risk of the subject.
  6. Patients with serious social and mental disability, inability/restriction of legal capacity;
  7. Refusal to sign informed consent;
  8. Patients with severe liver disease (eg Child Pugh score ≥ C, AST> 5 times upper limit of normal );
  9. Patients with severe renal insufficiency (estimated glomerular filtration rate ≤30mL / min / 1.73m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboConventional treatment plus placebo
Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs)BM-MSCsConventional treatment plus BM-MSCs
Primary Outcome Measures
NameTimeMethod
Changes of oxygenation index (PaO2/FiO2)At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

Evaluation of pneumonia improvement

Side effects in the BM-MSCs treatment groupBaseline through 6 months

Proportion of participants with treatment-related adverse events

Secondary Outcome Measures
NameTimeMethod
CT ScanAt baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

Evaluation of pneumonia improvement

Rate of mortality within 28-daysFrom baseline to day 28

Marker for efficacy

Changes of C-reactive proteinAt baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

Markers of Infection

Clinical outcomeAt baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.

Hospital stayBaseline through 6 months

days of the patients in hospital

Changes in viral loadAt baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

(deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)

Changes of CD4+, CD8+ cells count and concentration of cytokinesAt baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

Immunological status

Trial Locations

Locations (1)

Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University

🇨🇳

Guangzhou, Guangdong, China

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