Safety and Feasibility of Allogenic MSC in the Treatment of COVID-19

Phase 1

• Conditions: Sars-CoV2; COVID-19
• Interventions: Biological: Mesenchymal Stromal Cells infusion

• Registration Number: NCT04467047
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

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

Coronavirus-19 Disease (COVID-19), caused by the Sars-Cov-2 virus, which occurs as a growing pandemic in early 2020 and currently represents an emergency state worldwide. Several reports have shown that the first step in the pathogenesis of Sars-Cov-2 is the recognition of the angiotensin I converting enzyme (ACE2) receptor by the virus. This ACE2 receptor is widely distributed on the surface of human cells, especially as type II alveolar cells and capillary endothelium, however bone marrow, lymph nodes, thymus and spleen are known as immune cells, such as T and lymphocytes. B and macrophages, are negatives to ACE2. These results suggest that immunotherapy can be used to treat infected patients. However, an immunomodulatory capacity cannot be so strong, if just one or two major immunological factors used, as the virus can cause a "cytokine storm", such as IL-2, IL-6, IL-7, GSCF, IP10 , MCP1, MIP1A and TNFα, followed by edema, gas exchange dysfunction, acute respiratory distress syndrome, cardiac injury and secondary infection that can lead to death. Therefore, avoiding a "cytokine storm" may be the key to treating patients infected with Sars-Cov-2. Mesenchymal stem cells (MSCs), due to their potential for immunomodulatory activity, can have beneficial effects in preventing or attenuating the cytokine storm. Because MSCs have been widely used in cell therapy, from basic research to clinical trials. Safety and efficacy have been clearly documented in several clinical trials, especially in immune-mediated inflammatory diseases, such as graft versus host disease (GVHD). The objective of the study is to verify the safety and feasibility of using allogeneic bone marrow mesenchymal stem cells in patients with SARS-CoV-2.

Study Timeline

• Status Verified: 2020-07
• Study First Submitted: 2020-07-07
• Study First Submitted QC: 2020-07-09
• Last Update Submitted: 2020-07-09
• Study First Posted: 2020-07-10
• Last Update Posted: 2020-07-10
• Study Start: 2020-07-25
• Primary Completion: 2020-10-30
• Study Completion: 2020-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain reaction (RT-PCR)
• The patient or legal donor agrees to participate in the study and signs the informed consent.
• Patients with orange or red criteria according to the score proposed by Liao et al (2020)

Exclusion Criteria

• Patient with pregnancy, are planning to become pregnant or breastfeeding
• Patients with malignant blood-borne diseases such as HIV or syphilis
• Not consenting for clinical trial
• Patients with other than orange or red criteria according to the score proposed by Liao et al (2020)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Mesenchymal Stromal Cells infusion	Intravenous 1\*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion

Primary Outcome Measures

Name	Time	Method
Overall survival	60 days	Assessment of Overall survival at 30 days post intervention

Secondary Outcome Measures

Name	Time	Method
Radiological improvement	60 days	Computed tomography Chest assesment will be done to assess improvement in radiological findings of COVID-19
Changes on inflammatory C-reactive protein	60 days	To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of C-reactive protein (mg/dL)
Hospital stay	60 days	days of the patients in hospital
Oxygenation index (PaO2/FiO2)	60 days	Evaluation of functional respiratory changes: PaO2 / FiO2 ratio
Improvement in Liao's score (2020)	60 days	Improvement in Liao's score (2020)
Time of COVID19 PCR negativity	28 days	PCR testing to check PCR negativity