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

NCT ID: NCT04753476

Last Updated: 2021-05-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-08

Study Completion Date

2022-03-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Covid-19 Cytokine Storm

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Secretome-MSCs (n=24)

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

Group Type EXPERIMENTAL

Injection of Secretome-MSCs

Intervention Type BIOLOGICAL

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

Standard treatment of Covid-19

Intervention Type DRUG

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

Control (n=24)

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

Group Type OTHER

Standard treatment of Covid-19

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type BIOLOGICAL

Standard treatment of Covid-19

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Provincial Government of Central Java, Indonesia

UNKNOWN

Sponsor Role collaborator

Stem Cell and Cancer Research Indonesia

NETWORK

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Agung Putra

Assoc. Prof. Dr. dr. Agung Putra, M.Si. Med

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Agung Putra, Assoc.Prof

Role: PRINCIPAL_INVESTIGATOR

Stem Cell and Cancer Research Indonesia

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

RSUD Bantul

Bantul, Central Java, Indonesia

Site Status RECRUITING

RS PKU Muhammadiyah Gamping

Yogyakarta, Central Java, Indonesia

Site Status RECRUITING

RS Primaya Bekasi Timur

Bekasi, Jakarta Special Capital Region, Indonesia

Site Status RECRUITING

Bhayangkara Hospital

Makassar, South Celebes, Indonesia

Site Status RECRUITING

Gatot Soebroto Army Hospital

Jakarta, , Indonesia

Site Status RECRUITING

Dr. Esnawan Antariksa Air Force Hospital

Jakarta, , Indonesia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Indonesia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Agung Putra, Assoc.Prof

Role: CONTACT

+628164251646

Bhirau Wilaksono, MD

Role: CONTACT

+6285277777824

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Yuni Iswati Raharjani, MD, Sp.P

Role: primary

0811274816

Agus Widyatmoko, MD, Sp.PD

Role: primary

+62813-2832-4539

Muhammad Irhamsyah, MD, Sp.KK

Role: primary

08114122999

Fajar Amansyah, MD, Sp.PD

Role: primary

+62853-4363-7775

Basuki Rachmad, MD, Sp.An KIC

Role: primary

+62852-2022-2519

Crispinus Adhi Suryo, MD, Sp.An

Role: primary

+62812-9578-192

Flora Eka Sari, MD, Sp.P

Role: backup

+62821-1447-7473

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 31986264 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32105632 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24781370 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30341012 (View on PubMed)

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: 10.1155/2020/1939768. eCollection 2020.

Reference Type RESULT
PMID: 33274176 (View on PubMed)

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.

Reference Type RESULT
PMID: 32747157 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

SCCR_Secretome

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Menstrual Blood Stem Cells in Severe Covid-19
NCT05019287 COMPLETED PHASE1/PHASE2
Pyridostigmine in Severe SARS-CoV-2 Infection
NCT04343963 UNKNOWN PHASE2/PHASE3
COVID-19 - Cytokine Storm
NCT04474067 UNKNOWN