Ignite Creation Date:
2024-05-06 @ 2:53 PM
Last Modification Date:
2024-10-26 @ 1:39 PM
Study NCT ID:
NCT04457609
Status:
UNKNOWN
Last Update Posted:
2020-07-07
First Post:
2020-05-27
Brief Title:
Administration of Allogenic UC-MSCs as Adjuvant Therapy for Critically-Ill COVID-19 Patients
Sponsor:
Indonesia University
Organization:
Indonesia University
Study Overview
Official Title:
Application of Umbilical Cord Mesenchymal Stem Cells as Adjuvant Therapy for Critically-Ill COVID-19 Patients
Status:
UNKNOWN
Status Verified Date:
2020-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Novel Coronavirus 2019nCoV or Severe Acute Respiratory Syndrome-Coronavirus-2 SARS-CoV-2 that causes Coronavirus Disease 2019 or known as Covid-19 has recently become a global health emergency since it was first detected in Wuhan the People Republic of China in December 2019 Since then the prevalence has rapidly increased worldwide In Indonesia by the end of April 2020 around 10000 patients have been tested positive for Covid-19 infection with a case fatality rate of around 8
The pathogenesis of Covid-19 is still under investigation and to our understanding ACE2 receptors in the alveoli serve as the binding site of the S-protein of envelope spike virus of SARS-CoV-2 TMPRSS2 enzyme aids the fusion between cell membrane and capsid of the virus allowing penetration of virus into the cell Vesicles containing virion fuse with cell membrane and released as new virions Cytopathic effect of the virus and its ability to overcome immune response determines the degree of infection
Differences in immunological profile among degrees of severity of Covid-19 may vary especially for the number of pro-inflammatory cytokines such as tumor necrosis factor alpha TNF-α interleukin IL-1 IL-6 IL-8 leukemia-inhibiting factors LIF immunological markers such as CXCR3CD4 CXCR3CD8 T cell and CXCR3 NK cells implying the ongoing cytokine storm The previous studies also found increasing number for infection markers such as procalcitonin ferritin and C-reactive protein The decreasing number of anti-inflammatory cytokines in such as IL-10 also supports this finding
Previous studies have shown immunomodulating and anti-inflammatory capacity of the mesenchymal stem cells MSCs MSCs contributed to the shifting of pro-inflammatory Th2 into anti-inflammatory Th2 One of the most recent study on the usage of MSCs on Covid-19 patients showed increased expression of leukemia inhibitory factor LIF which give rise to inhibitory effect of T lymphocyte and natural killer NK cell population Vascular epithelial growth factor VEGF is found increasing following MSCs administration which indicates the ability to improve the disrupted capillaries due to SARS-Cov-2 infection The ability of MSCs in differentiating to alveolar cells is proven by the presence of SPM and SPC2 surfactant proteins produced by type II alveolar cells MSCs are unable to be infected by SARS-CoV-2 since they dont have ACE2 receptors and TMPRSS2 enzyme
The pathogenesis of Covid-19 is still under investigation and to our understanding ACE2 receptors in the alveoli serve as the binding site of the S-protein of envelope spike virus of SARS-CoV-2 TMPRSS2 enzyme aids the fusion between cell membrane and capsid of the virus allowing penetration of virus into the cell Vesicles containing virion fuse with cell membrane and released as new virions Cytopathic effect of the virus and its ability to overcome immune response determines the degree of infection
Differences in immunological profile among degrees of severity of Covid-19 may vary especially for the number of pro-inflammatory cytokines such as tumor necrosis factor alpha TNF-α interleukin IL-1 IL-6 IL-8 leukemia-inhibiting factors LIF immunological markers such as CXCR3CD4 CXCR3CD8 T cell and CXCR3 NK cells implying the ongoing cytokine storm The previous studies also found increasing number for infection markers such as procalcitonin ferritin and C-reactive protein The decreasing number of anti-inflammatory cytokines in such as IL-10 also supports this finding
Previous studies have shown immunomodulating and anti-inflammatory capacity of the mesenchymal stem cells MSCs MSCs contributed to the shifting of pro-inflammatory Th2 into anti-inflammatory Th2 One of the most recent study on the usage of MSCs on Covid-19 patients showed increased expression of leukemia inhibitory factor LIF which give rise to inhibitory effect of T lymphocyte and natural killer NK cell population Vascular epithelial growth factor VEGF is found increasing following MSCs administration which indicates the ability to improve the disrupted capillaries due to SARS-Cov-2 infection The ability of MSCs in differentiating to alveolar cells is proven by the presence of SPM and SPC2 surfactant proteins produced by type II alveolar cells MSCs are unable to be infected by SARS-CoV-2 since they dont have ACE2 receptors and TMPRSS2 enzyme
Detailed Description:
This study is a double blind randomized control trial RCT This study will be concluded in 2 months from May to July 2020 from subject selection to the end of follow up Research subjects are obtained consecutively from Covid-19 patients who receive care in the intensive care unit ICU across four Covid-19 referral hospitals including Persahabatan Hospital Sulianti Saroso Center for Infectious Disease Cipto Mangunkusumo General Hospital and Universitas Indonesia Hospital with 10 subjects obtained from each hospital and total 40 subjects for this RCT Subjects from each hospitals are divided into control and experimental groups Subject belongs to the control group will receive standardized therapy consisting of oseltamivir and azithromycin whereas subjects in the experimental group will receive MSCs infusion in addition to standardized therapy
Subject Criteria Inclusion Criteria for MSC Donor from Umbilical Cord
Umbilical cord is collected from elective caesarean section from a fullterm pregnancies without any complication and free from HIV Hepatitis B C D virus Cytomegalovirus Rubella Virus and free from fungal and bacterial contamination
Informed consent all of the subjects must be filled and signed up before ruled in this study
As soon as after delivery the umbilical cord is collected and processed in sterile specimen 09 NaCl at 4oC for 8 hours The umbilical cord transported to the laboratory and cultured in GMP lab at Stem Cells Medical Technology Integrated Service Unit Cipto Mangunkusumo Hospital Cellular viability and proliferation are evaluated after cell characterization test by flow cytometer
Sterility tests are done three times to ensure cellular sterility Subjects will receive MSCs through infusion through intravenous for 1 hour following the administration of diphenhydramine and anticoagulant to prevent clotting
Following the MSCs administration monitoring at the patients is carried out every day whereas laboratory testing for basic parameters complete blood count differential count blood gas analysis C-reactive protein SGOTSGPT ASTALT UreumCreatinine eGFR electrolyte procalcitonin albumin total bilirubin D-Dimer fibrinogen troponin I and proBNP are carried out every three days Cytokine levels are measured before the administration and 7th day after the administration Chest radiography is carried out every three days
Subject Criteria Inclusion Criteria for MSC Donor from Umbilical Cord
Umbilical cord is collected from elective caesarean section from a fullterm pregnancies without any complication and free from HIV Hepatitis B C D virus Cytomegalovirus Rubella Virus and free from fungal and bacterial contamination
Informed consent all of the subjects must be filled and signed up before ruled in this study
As soon as after delivery the umbilical cord is collected and processed in sterile specimen 09 NaCl at 4oC for 8 hours The umbilical cord transported to the laboratory and cultured in GMP lab at Stem Cells Medical Technology Integrated Service Unit Cipto Mangunkusumo Hospital Cellular viability and proliferation are evaluated after cell characterization test by flow cytometer
Sterility tests are done three times to ensure cellular sterility Subjects will receive MSCs through infusion through intravenous for 1 hour following the administration of diphenhydramine and anticoagulant to prevent clotting
Following the MSCs administration monitoring at the patients is carried out every day whereas laboratory testing for basic parameters complete blood count differential count blood gas analysis C-reactive protein SGOTSGPT ASTALT UreumCreatinine eGFR electrolyte procalcitonin albumin total bilirubin D-Dimer fibrinogen troponin I and proBNP are carried out every three days Cytokine levels are measured before the administration and 7th day after the administration Chest radiography is carried out every three days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None