Menstrual Blood Stem Cells in Severe Covid-19

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Cytokine Storm
• Intervention / Treatment: Biological: Allogeneic human menstrual blood stem cells secretome; Other: Intravenous saline injection

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Avicenna Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Menstrual blood stem cell secretome group; Intravenous Allogeneic Menstrual Blood Stem Cells Secretome injection+Routine treatment	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.
Placebo Comparator: Control group; Intravenous saline injection (Placebo)+Routine treatment	Other: Intravenous saline injection; Intravenous saline injection in addition to standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reactions incidence	The proportion of participants with treatment-related Adverse Event as assessed by CTCAE v5.0.	Day 0 - 28
Time to clinical improvement	Days from administration of the Investigational Product for improvement	Day 0 - 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Lung Involvement	Side effects measured by Chest Readiograph Side effects measured by Chest Readiograph	Day 0 - 28
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
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

Collaborators and Investigators

• Sponsor: Avicenna Research Institute
• Collaborators: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Mina Fathi Kazerooni, MD, PhD, Nanobiotechnology Research Center Avicenna Research Institute, ACECR, TEHRAN, IRAN; Study Chair: Ali Dehghan-Manshadi, MD, Department of Infectious Diseases and Tropical Medicine - Iranian Research Center for HIV/AIDS,TUMS; Study Director: Samrand Fattah-Ghazi, MD, Tehran University of Medical Science (TUMS); Study Chair: Somaieh Kazemnejad, PhD, Nanobiotechnology Research Center Avicenna Research Institute, ACECR, TEHRAN, IRAN

Publications and helpful links

General Publications

• Fathi-Kazerooni M, Fattah-Ghazi S, Darzi M, Makarem J, Nasiri R, Salahshour F, Dehghan-Manshadi SA, Kazemnejad S. Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II. Stem Cell Res Ther. 2022 Mar 7;13(1):96. doi: 10.1186/s13287-022-02771-w.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2021
• Primary Completion (Actual): May 21, 2021
• Study Completion (Actual): June 9, 2021

Study Registration Dates

• First Submitted: July 3, 2021
• First Submitted That Met QC Criteria: August 22, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: August 28, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: covid-19; mesenchymal stem cells; secretome; menstrual blood stem cell
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Shock; COVID-19; Cytokine Release Syndrome
• Other Study ID Numbers: 990308-026; 99/3436 (Other Grant/Funding Number: Avicenna Research Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No