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

Covid-19 Clinical Trial

Official title:

The Effect of Secretome of Hypoxia-Mesenchymal Stem Cells in Improving Survival of Severe Covid-19 Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04753476
• Other study ID #: SCCR_Secretome
• Status: Recruiting
• Phase: Phase 2
• Start date: June 8, 2020
• Est. completion date: March 1, 2022

Study information

• Verified date: May 2021
• Source: Stem Cell and Cancer Research Indonesia
• Contact: Agung Putra, Assoc.Prof
• Phone: +628164251646
• Email: dr.agungptr[@]gmail.com
• 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 hypoxia-mesenchymal stem cells. The improvement in 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: March 1, 2022
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Covid-19
• Cytokine Storm
• Hypoxia

Intervention

Biological:
• Injection of Secretome-MSCs
Injection of Hypoxic Secretome-MSCs intramuscular (deltoideus) : Day 1: 1 cc every 12 hours Day 2: 1 cc every 12 hours Day 3: 1 cc every 12 hours

Drug:
• Standard treatment of Covid-19
Patients will be given Standard treatment of Covid-19 which accordance with National protocol

Locations

Country	Name	City	State
Indonesia	RSUD Bantul	Bantul	Central Java
Indonesia	RS Primaya Bekasi Timur	Bekasi	Jakarta
Indonesia	Dr. Esnawan Antariksa Air Force Hospital	Jakarta
Indonesia	Gatot Soebroto Army Hospital	Jakarta
Indonesia	Bhayangkara Hospital	Makassar	South Celebes
Indonesia	RS PKU Muhammadiyah Gamping	Yogyakarta	Central Java

Sponsors (2)

Lead Sponsor	Collaborator
Stem Cell and Cancer Research Indonesia	Provincial Government of Central Java, Indonesia

Country where clinical trial is conducted

Indonesia, 

References & Publications (6)

Chen L, Xu Y, Zhao J, Zhang Z, Yang R, Xie J, Liu X, Qi S. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice. PLoS One. 2014 Apr 29;9(4):e96161. doi: 10.1371/journal.pone.0096161. eCollection 2014. Erratum in: PLoS One. 2015;10(12):e0145565. — View Citation

Haraszti RA, Miller R, Stoppato M, Sere YY, Coles A, Didiot MC, Wollacott R, Sapp E, Dubuke ML, Li X, Shaffer SA, DiFiglia M, Wang Y, Aronin N, Khvorova A. Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity. Mol Ther. 2018 Dec 5;26(12):2838-2847. doi: 10.1016/j.ymthe.2018.09.015. Epub 2018 Sep 22. — View Citation

Harrell CR, Jovicic BP, Djonov V, Volarevic V. Therapeutic Potential of Mesenchymal Stem Cells and Their Secretome in the Treatment of SARS-CoV-2-Induced Acute Respiratory Distress Syndrome. Anal Cell Pathol (Amst). 2020 Nov 20;2020:1939768. doi: 10.1155/ — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:. — View Citation

Johnson BS, Laloraya M. A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization. Cytokine Growth Factor Rev. 2020 Aug;54:32-42. doi: 10.1016/j.cytogfr.2020.06.014. Epub 2020 Jul 1. Review. — View Citation

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24. Erratum in: Lancet Respir Med. 2020 Apr;8(4):e26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in patients clinical manifestation	mild, moderate, or severe	1 months
Primary	Need for a ventilator	There are respiratory variables that made severe Covid-19 patients previously stable but worsened, requiring a ventilator; Divided into two categories: It is necessary; No need	1 months
Primary	Duration of using a ventilator	Duration of use of a ventilator from the day of intubation to the day of extubation	1 months
Primary	Length of stay	The length of stay from the first treatment to the patient's final outcome, recovery, or death	1 months
Primary	Routine blood profile	Obtained from patients before and after treatment	2 weeks
Primary	CRP	Obtained from patients before and after treatment	2 weeks
Primary	D-dimer	Obtained from patients before and after treatment	2 weeks
Primary	Blood Gas Analisis (BGA)	Obtained from patients before and after treatment	2 weeks
Primary	Photo thorax	Obtained from patients before and after treatment	2 weeks
Secondary	Survival	Death	2 months