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

Coronavirus Disease 2019 (COVID-19) Clinical Trial

Official title:

Safety and Efficacy of Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells in Severe Patients With Coronavirus Disease 2019 (COVID-19): A Phase 1/2 Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04346368
• Other study ID #: SC-2020-01
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2020
• Est. completion date: December 2020

Study information

• Verified date: April 2020
• Source: Guangzhou Institute of Respiratory Disease
• Contact: Shiyue Li, MD
• Phone: 86-20-83062885
• Email: lishiyue[@]188.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Disease 2019 (COVID-19)
• Coronavirus Infections

Intervention

Biological:
• BM-MSCs
Participants will receive conventional treatment plus BM-MSCs(1*10E6 /kg body weight intravenously at Day 1).
• Placebo
Placebo

Locations

Country	Name	City	State
China	Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (4)

Lead Sponsor	Collaborator
Guangzhou Institute of Respiratory Disease	Guangzhou Cellgenes Biotechnology Co.,Ltd, Guangzhou Eighth People's Hospital, Tongji Hospital, Huazhong University of Science & Technology

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of oxygenation index (PaO2/FiO2)	Evaluation of pneumonia improvement	At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
Primary	Side effects in the BM-MSCs treatment group	Proportion of participants with treatment-related adverse events	Baseline through 6 months
Secondary	Clinical outcome	Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.	At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
Secondary	Hospital stay	days of the patients in hospital	Baseline through 6 months
Secondary	CT Scan	Evaluation of pneumonia improvement	At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
Secondary	Changes in viral load	(deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)	At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
Secondary	Changes of CD4+, CD8+ cells count and concentration of cytokines	Immunological status	At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
Secondary	Rate of mortality within 28-days	Marker for efficacy	From baseline to day 28
Secondary	Changes of C-reactive protein	Markers of Infection	At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.