Clinical trial NCT05019287: Menstrual Blood Stem Cells in Severe Covid-19
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Covid19
Cytokine Storm
Keywords: mesenchymal stem cells
menstrual blood stem cell
secretome
covid-19
Lead sponsor: Avicenna Research Institute
Sponsor class: OTHER
Collaborators: name: Tehran University of Medical Sciences
First posted: 2021-08-24
Enrollment: 29
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. Biological: allogeneic human menstrual blood stem cells secretome Intravenous injection of 5 ml menstrual blood stem cells secretome on day 1, day 2, day 3, day 4, and day 5, based on the routine treatment of COVID-19
2. Other: Intravenous saline injection (Placebo) Intravenous injection of 5ml of 0.9% saline on day 1, day 2, day 3, day 4, and day 5, based on the routine treatment of COVID-19
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse reactions incidence
timeFrame: Day 0 - 28
measure: Time to clinical improvement
timeFrame: Day 0 - 28
Secondary outcomes:
measure: Assessment of serum CRP (mg/L) levels
timeFrame: Days 0, 5, 10, 14, and 28
measure: Assessment of serum LDH (U/L) levels
timeFrame: Days 0, 5, 10, 14, and 28
measure: Assessment of serum Ferritin (ng/ml) levels
timeFrame: Days 0, 5, 10, 14, and 28
measure: Assessment of serum D-dimer (microgr/ml) levels
timeFrame: Days 0, 5, 10, 14, and 28
measure: Immunological changes on CD4+ T and CD8+ T
timeFrame: Days 0, 5, 10, 14, and 28
measure: Lung Involvement
timeFrame: Day 0 - 28
measure: Changes in Inflammatory cytokine IL 6
timeFrame: Days 0, 5, 10, 14, and 28
measure: Changes in anti-Inflammatory cytokine IL10
timeFrame: Days 0, 5, 10, 14, and 28
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Avicenna Research Institute
Study officials:
affiliation: Nanobiotechnology Research Center Avicenna Research Institute, ACECR, TEHRAN, IRAN
name: Mina Fathi Kazerooni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Infectious Diseases and Tropical Medicine - Iranian Research Center for HIV/AIDS,TUMS
name: Ali Dehghan-Manshadi, MD
role: STUDY_CHAIR
affiliation: Tehran University of Medical Science (TUMS)
name: Samrand Fattah-Ghazi, MD
role: STUDY_DIRECTOR
affiliation: Nanobiotechnology Research Center Avicenna Research Institute, ACECR, TEHRAN, IRAN
name: Somaieh Kazemnejad, PhD
role: STUDY_CHAIR
References:
citation: 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.