Menstrual Blood Stem Cells in Severe Covid-19

Covid19 Clinical Trial

Official title:

Safety and Efficacy Study of Allogeneic Human Menstrual Blood Stem Cells Secretome to Treat Severe Covid-19 Patients, Clinical Trial Phase I&II

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05019287
• Other study ID #: 990308-026
• Secondary ID: 99/3436
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 17, 2021
• Est. completion date: June 9, 2021

Study information

• Verified date: August 2021
• Source: Avicenna Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 9, 2021
• Est. primary completion date: May 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Covid19
• Cytokine Storm

Intervention

Biological:
• Allogeneic human menstrual blood stem cells secretome
This COVID-19 Study intervention consists of Intravenous Allogeneic human menstrual blood stem cell (MenSC) secretome injection in addition to standard care. The MenSC were characterized as CD90+, CD73+, CD105+, and CD45-based on multiparameter flow cytometry.

Other:
• Intravenous saline injection
Intravenous saline injection in addition to standard care

Locations

Country	Name	City	State
Iran, Islamic Republic of	Avicenna Research Institute	Tehran

Sponsors (2)

Lead Sponsor	Collaborator
Avicenna Research Institute	Tehran University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse reactions incidence	The proportion of participants with treatment-related Adverse Event as assessed by CTCAE v5.0.	Day 0 - 28
Primary	Time to clinical improvement	Days from administration of the Investigational Product for improvement	Day 0 - 28
Secondary	Assessment of serum CRP (mg/L) levels	To evaluate the anti-inflammatory effect of the proposed treatment an assessment of the inflammatory markers	Days 0, 5, 10, 14, and 28
Secondary	Assessment of serum LDH (U/L) levels	To evaluate the anti-inflammatory effect of the proposed treatment an assessment of the inflammatory markers	Days 0, 5, 10, 14, and 28
Secondary	Assessment of serum Ferritin (ng/ml) levels	To evaluate the anti-inflammatory effect of the proposed treatment an assessment of the inflammatory markers	Days 0, 5, 10, 14, and 28
Secondary	Assessment of serum D-dimer (microgr/ml) levels	To evaluate the anti-inflammatory effect of the proposed treatment an assessment of the inflammatory markers	Days 0, 5, 10, 14, and 28
Secondary	Immunological changes on CD4+ T and CD8+ T	Evaluate immune system improvement with flow cytometry to analyze patients' immune cells	Days 0, 5, 10, 14, and 28
Secondary	Lung Involvement	Side effects measured by Chest Readiograph Side effects measured by Chest Readiograph	Day 0 - 28
Secondary	Changes in Inflammatory cytokine IL 6	To assess the anti-inflammatory effect of the proposed treatment an assessment of the levels of IL6 in plasma.	Days 0, 5, 10, 14, and 28
Secondary	Changes in anti-Inflammatory cytokine IL10	To assess the anti-inflammatory effect of the proposed treatment an assessment of the levels of IL10 in plasma.	Days 0, 5, 10, 14, and 28