Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06511024
Status:
COMPLETED
Last Update Posted:
None
First Post:
2020-04-16
Brief Title:
Profiling the Inflammatory Cascade of COVID-19
Sponsor:
None
Organization:
None
Study Overview
Official Title:
CASCADE Profiling the Inflammatory Cascade of COVID-19
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CASCADE
Brief Summary:
COVID-19 is a new and poorly understood virus It is imperative that the scientific community develops an understanding of the viral mechanisms and human immunological response in order to develop effective therapies and assess their efficacy
This research study is being initiated in response to the ongoing COVID-19 pandemic and will provide much needed insight into the temporal immune response which can lead to rapid respiratory failure in infected patients
This research study is being initiated in response to the ongoing COVID-19 pandemic and will provide much needed insight into the temporal immune response which can lead to rapid respiratory failure in infected patients
Detailed Description:
The immuno-inflammatory cascade is essential to define in COVID-19 patients to develop an intervention strategy to abrogate respiratory failure For this study four groups of patients have been identified to inform disease characterisation
Patients in the community
Patients at hospital admission
Rapidly deteriorating patients
Ventilated critically ill patients There is an urgent need to elucidate the dynamic peripheral blood signature including neutrophil monocyte lymphocyte and soluble mediators Indeed recent data suggest that activation and subsequent exhaustion of cytotoxic T cells and emergence of GM-CSF CD4 T cells and inflammatory monocytes and macrophages in blood and BAL123 are associated with severe pathology in COVID-19 patients however the fine kinetics of changes in these populations relative to disease progression are unknown
In this study samples will be obtained from NHS Lothian patients in both primary care and hospital settings who have tested positive for COVID-19 infection Once consented blood samples and where possible surplus clinical samples will be obtained from participants at defined time-points through the duration of their disease Participants who rapidly deteriorate during their hospital admission will provide smaller more frequent blood samples to permit profiling of the immunologicalinflammatory response during deterioration
Patients without COVID-19 but of comparable age and comorbid status will act as controls
In-house assays will be used to measure and phenotype circulating immune cells their activation status and cytokine production focusing primarily on polymorphonuclear leukocytes mononuclear phagocytes and lymphocytes from peripheral blood samples obtained from participants at different stages of COVID-19 disease
Blood and other clinical samples including but not limited to Bronchoalveolar Lavage BAL bronchoabsorption will undergo laboratory analysis including but not limited to whole blood cytokine release assays inflammatory biomarkers and cell numbers measurement of cytokines flow cytometric cell analysis and staining of cells for markers
Results will inform the identification of optimized biomarkers timing of interventions and lead prioritisation of pharmaceutical assets for experimental medicine studies or assays for use in high throughput automated screens of compound libraries to modulate observed phenotypes and profile the inflammatory pathway It will build from and complement emerging data from other national or international studies eg ISARIC 4C but will be distinct since it informs a specific translational study platform which requires greater depth of phenotyping and more precise kinetic analysis to inform design of early clinical studies of repurposed immunomodulating therapeutics It is intended this will accelerate the linking of basic mechanistic information with drug targets for development and assessment of COVID-19 therapies Research materials and results will be also be used to develop novel diagnostics and prognostic approaches that can help identify high risk patients who need higher level of monitoring or care and more fully define susceptibility and risk
Patients in the community
Patients at hospital admission
Rapidly deteriorating patients
Ventilated critically ill patients There is an urgent need to elucidate the dynamic peripheral blood signature including neutrophil monocyte lymphocyte and soluble mediators Indeed recent data suggest that activation and subsequent exhaustion of cytotoxic T cells and emergence of GM-CSF CD4 T cells and inflammatory monocytes and macrophages in blood and BAL123 are associated with severe pathology in COVID-19 patients however the fine kinetics of changes in these populations relative to disease progression are unknown
In this study samples will be obtained from NHS Lothian patients in both primary care and hospital settings who have tested positive for COVID-19 infection Once consented blood samples and where possible surplus clinical samples will be obtained from participants at defined time-points through the duration of their disease Participants who rapidly deteriorate during their hospital admission will provide smaller more frequent blood samples to permit profiling of the immunologicalinflammatory response during deterioration
Patients without COVID-19 but of comparable age and comorbid status will act as controls
In-house assays will be used to measure and phenotype circulating immune cells their activation status and cytokine production focusing primarily on polymorphonuclear leukocytes mononuclear phagocytes and lymphocytes from peripheral blood samples obtained from participants at different stages of COVID-19 disease
Blood and other clinical samples including but not limited to Bronchoalveolar Lavage BAL bronchoabsorption will undergo laboratory analysis including but not limited to whole blood cytokine release assays inflammatory biomarkers and cell numbers measurement of cytokines flow cytometric cell analysis and staining of cells for markers
Results will inform the identification of optimized biomarkers timing of interventions and lead prioritisation of pharmaceutical assets for experimental medicine studies or assays for use in high throughput automated screens of compound libraries to modulate observed phenotypes and profile the inflammatory pathway It will build from and complement emerging data from other national or international studies eg ISARIC 4C but will be distinct since it informs a specific translational study platform which requires greater depth of phenotyping and more precise kinetic analysis to inform design of early clinical studies of repurposed immunomodulating therapeutics It is intended this will accelerate the linking of basic mechanistic information with drug targets for development and assessment of COVID-19 therapies Research materials and results will be also be used to develop novel diagnostics and prognostic approaches that can help identify high risk patients who need higher level of monitoring or care and more fully define susceptibility and risk
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None