Clinical trial NCT04467047: Safety and Feasibility of Allogenic MSC in the Treatment of COVID-19
Official title: Safety and Feasibility of Allogenic Mesenchymal Stromal Cells in the Treatment of COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: COVID-19
Sars-CoV2
Keywords: Mesenchymal Stromal Cells
COVID-19
Sars-CoV2
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2020-07-10
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall survival
timeFrame: 60 days
Secondary outcomes:
measure: Changes on inflammatory C-reactive protein
timeFrame: 60 days
measure: Hospital stay
timeFrame: 60 days
measure: Oxygenation index (PaO2/FiO2)
timeFrame: 60 days
measure: Improvement in Liao's score (2020)
timeFrame: 60 days
measure: Radiological improvement
timeFrame: 60 days
measure: Time of COVID19 PCR negativity
timeFrame: 28 days
Other outcomes:
Locations:
Study officials:
affiliation: Hospital de Clinicas de Porto Alegre
name: Lucia Silla, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: