Treatment of Severe COVID-19 Patients Using Secretome of Hypoxia-Mesenchymal Stem Cells in Indonesia

Stem Cell and Cancer Research Indonesia

Status and phase: Unknown; Phase 2

Conditions: Cytokine Storm; Covid-19

Treatments: Drug: Standard treatment of Covid-19; Biological: Injection of Secretome-MSCs

Study type: Interventional

Funder types: NETWORK; Other

Identifiers

NCT04753476

SCCR_Secretome

Details and patient eligibility

About

In this randomized controlled trial (RCT), severe cases of COVID-19 infection will be treated with secretome of hypoxia-mesenchymal stem cells. The improvement in 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 reported a correlation between disease severity and the release of excessive proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), IL-6, IL-1, IFN-Υ, IFN-Υ-induced protein 10 (IP10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1a (MIP-1a), and granulocyte-colony stimulating factor (G-CSF). This finding was confirmed by the high level of plasma cytokines found in most severe COVID-19 patients associated with extensive lung damage. Therefore, finding an effective therapeutic option to control the devastating cytokine storm of COVID-19 and regenerate the damaged lung is crucial.

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: 48 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients whose clinical and laboratory test results have a positive diagnosis of Covid-19.

2. Patients who are willing to participate as subjects in the study by signing the informed content.

3. Criteria for Berlin to enter ARDS (moderate and severe) with or without a ventilator:

   • PaO2 / FiO2: moderate 100-200
   • PaO2 / FiO2: severe <100

4. One or more comorbid history

5. SOFA score

Exclusion criteria

1. The Covid19 patient has fibrosis (based on the results of the chest X-ray or CT chest)
2. ECOG 4 performance status, decreased irreversible consciousness, brain stem death.
3. Severe NYHA III / IV heart failure
4. Pregnant women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 2 patient groups

Secretome-MSCs (n=24)

Experimental group

Description:

This group will be given Covid-19 standard therapy with intramuscular Hypoxic S-MSC secretome

Treatment:

Drug: Standard treatment of Covid-19

Biological: Injection of Secretome-MSCs

Control (n=24)

Other group

Description:

This group will receive standard Covid-19 therapy with the best supportive care

Treatment:

Drug: Standard treatment of Covid-19