Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe COVID-19 Patients

Study Overview
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Brief Summary
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This clinical trial is set out to evaluate the safety and efficacy of allogeneic human dental pulp mesenchymal stem cells in the treatment of severe pneumonia caused by COVID-19; to explore the effects of human dental pulp mesenchymal stem cells in the treatment of severe pneumonia of COVID-19 in terms of reducing mortality and improving clinical prognosis; and to discover a new therapeutic strategy for COVID-19 using allogeneic human dental pulp mesenchymal stem cells.

Detailed Description
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This clinical trial is set out to evaluate the followings: the safety and efficacy of allogeneic human dental pulp mesenchymal stem cells in the treatment of severe pneumonia caused by COVID-19; to explore the effects of human dental pulp mesenchymal stem cells in the treatment of severe pneumonia of COVID-19 in terms of reducing mortality and improving clinical prognosis; and to discover a new therapeutic strategy for COVID-19 using allogeneic human dental pulp mesenchymal stem cells.

Official Title
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Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe Pneumonia of COVID-19：a Single-center, Prospective, Randomised Clinical Trial

Conditions
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COVID-19

Intervention / Treatment
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* Biological: allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC)
* Other: Intravenous saline injection (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 years; Voluntarily participate in this clinical trial and sign off informed consent form; Diagnosed with severe pneumonia of COVID: respiratory distress, RR >30 times / min; resting oxygen saturation of 93% or less; arterial partial pressure of oxygen / oxygen concentration 300mmHg; SARS-CoV-2 nucleic acid test was positive. Chest imaging confirm COVID-19 featured lesions in lung. Exclusion Criteria: Receive any clinical trial drug treatment for COVID-2019 within 30 days before the screening assessment; Severe liver disease (e.g., Child Pugh score >=C or AST> 5 times of the upper limit); Patients with known severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis; Co-infection of HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses; Female patients who have no sexual protection in the last 30 days prior to the screening assessment; Pregnant or lactating women or women using estrogen contraception; Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period; Other conditions that the researchers consider not suitable for participating in this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hDPSCs group<br>Routine treatment + Intravenous injection of human dental pulp stem cells | Biological: allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC)<br>* Intravenous injection of 3.0x10e7 human dental pulp stem cells solution (30ml) on day 1, day 4 and day 7, based on routine treatment of COVID-19<br>|
| Placebo Comparator: Control group<br>Routine treatment + Intravenous saline injection (Placebo) | Other: Intravenous saline injection (Placebo)<br>* Intravenous injection of 3ml of 0.9% saline on day 1, day 4 and day 7, based on routine treatment of COVID-19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTCI | Time to Clinical Improvement | 1-28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung lesion | Lung Lesion by CT | 1-28 days | 
| Immune function | Th1 cytokines: IL-1β, IL- 2, TNF-a, ITN-γ; Th2 cytokines: IL- 4, IL- 6, IL- 10; Immunoglobulins: IgA, IgG, IgM, and total IgE; Lymphocyte counts: CD3+, CD4+, CD8+, CD16+,CD19+, CD56+. | 1-28 days | 
| Time of SARS-CoV-2 clearance | Time of SARS-CoV-2 test turns negative | 1-28 days | 
| Blood test | Blood cell count and classification | 1-28 days | 
| SPO2 | Pulse oximetry | 1-28 days | 
| RR | Respiratory rate | 1-28 days | 
| Body temperature | Body temperature | 1-28 days | 
| Side effects in the treatment group | Number of the included patients with hDPSCs-related adverse events, e.g. liver or kidney function failure | 1-28 days | 
| C-reactive protein (mg/L) | C-reactive protein in microgram per litre | 1-28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cronovirus, Human Dental Pulp Stem Cells, Dental Stem Cell Banking