Menstrual Blood Stem Cells in Severe Covid-19

Avicenna Research Institute

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cytokine Storm

Covid19

Treatments

Biological: Allogeneic human menstrual blood stem cells secretome

Other: Intravenous saline injection

Study type

Interventional

Funder types

Other

Identifiers

NCT05019287

99/3436 (Other Grant/Funding Number)

990308-026

Details and patient eligibility

About

In this randomized controlled trial (RCT), severe cases of COVID-19 infection will be treated with secretome of menstrual blood stem cells. The improvement in the clinical, laboratory and radiological manifestations will be evaluated in treated patients compared with the control group.

Full description

The devastating effect of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) infection is caused by a robust cytokine storm that leads to lung tissue damage. Several studies have found that the severity of the disease is correlated with the release of excessive proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This finding was confirmed by the high level of plasma cytokines found in the most severe COVID-19 patients associated with extensive lung damage. As a result, it is essential to find an effective treatment option to control the devastating cytokine storm of COVID-19 and regenerate the damaged lung. Although mesenchymal stem cells are a powerful tool for clinical applications, they have limits in terms of administration, safety, and variability of therapeutic response. It is interesting to note that the MSC secretome composed of cytokines, chemokines, growth factors, proteins, and extracellular vesicles could be a valid alternative to their use. It is not only easier to preserve, transfer and produce the secretome, but also safer to administer.

Previous studies reported that the hypoxic condition of MSCs could enhance the release of their active soluble molecules known as Secretome-MSCs (S-MSCs), such as IL-10 and TGF-β that useful in alleviating inflammation. Moreover, they could also increase the expression of growth factors such as VEGF and PDGF that accelerate lung injury improvement. These active molecules could potentially serve as a biological therapeutic agent for treating the severe SARS-CoV-2 infection. According to recent studies, we successfully isolated the S-MSCs from their culture medium using tangential flow filtration (TFF) strategy with several molecular weight cut-off category. This study investigated the clinical outcomes of severe COVID-19 patients with several comorbidities treated with S-MSCs in Indonesia.

Enrollment

29 patients

Sex

All

Ages

25 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients whose clinical and laboratory test results have a positive diagnosis of Covid-19.
Patients who are willing to participate as subjects in the study by signing the informed content.
Diagnosed with severe pneumonia of COVID: respiratory distress, RR >30 times/min; resting oxygen saturation of 90% or less; arterial partial pressure of oxygen / oxygen concentration ≤300mmHg; Pulmonary infiltration more than 50% in 24 to 48 hours
SARS-CoV-2 nucleic acid test was positive.

Exclusion criteria

History of drug reactions or allergies
Pneumonia caused by bacteria, Mycoplasma, Chlamydia, Legionella, fungi, or other viruses
Airway obstruction due to lung cancer or unknown factors
Carcinoid syndrome
History of epilepsy and long-term use of anticonvulsant drugs during the last 3 years
History of long-term use of immunosuppressive drugs
History of chronic respiratory illness that requires long-term oxygen therapy
The patient is on blood or peritoneal dialysis
Creatinine clearance <15 ml / min
Moderate to severe liver disease (Child-Pugh score> 12)
History of deep vein thrombosis (DVT) or pulmonary embolism over the past 3 years
Being under ECMO or high-frequency oscillatory ventilation support
Diagnostic of HIV, hepatitis B, and syphilis
Pregnant or lactating women
Lack of consciousness and inability to provide informed consent by the patient