Menstrual Blood Stem Cells in Severe Covid-19

NCT ID: NCT05019287

Last Updated: 2021-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-17
• Study Completion Date: 2021-06-09

Brief 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.

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.

Conditions

Covid19; Cytokine Storm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Menstrual blood stem cell secretome group

Intravenous Allogeneic Menstrual Blood Stem Cells Secretome injection+Routine treatment

Group Type: EXPERIMENTAL

Allogeneic human menstrual blood stem cells secretome

Intervention Type: BIOLOGICAL

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.

Control group

Intravenous saline injection (Placebo)+Routine treatment

Group Type: PLACEBO_COMPARATOR

Intravenous saline injection

Intervention Type: OTHER

Intravenous saline injection in addition to standard care

Interventions

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.

Intervention Type: BIOLOGICAL

Intravenous saline injection

Intravenous saline injection in addition to standard care

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tehran University of Medical Sciences

OTHER

Sponsor Role: collaborator

Avicenna Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mina Fathi Kazerooni, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nanobiotechnology Research Center Avicenna Research Institute, ACECR, TEHRAN, IRAN

Ali Dehghan-Manshadi, MD

Role: STUDY_CHAIR

Department of Infectious Diseases and Tropical Medicine - Iranian Research Center for HIV/AIDS,TUMS

Samrand Fattah-Ghazi, MD

Role: STUDY_DIRECTOR

Tehran University of Medical Science (TUMS)

Somaieh Kazemnejad, PhD

Role: STUDY_CHAIR

Nanobiotechnology Research Center Avicenna Research Institute, ACECR, TEHRAN, IRAN

Locations

Avicenna Research Institute

Tehran, , Iran

Countries

Iran

References

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.

Reference Type: DERIVED

PMID: 35255966 (View on PubMed)

Other Identifiers

99/3436

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

990308-026

Identifier Type: -

Identifier Source: org_study_id