Ignite Creation Date:
2024-05-06 @ 10:52 AM
Last Modification Date:
2024-10-26 @ 12:37 PM
Study NCT ID:
NCT03379207
Status:
RECRUITING
Last Update Posted:
2023-12-18
First Post:
2017-12-15
Brief Title:
Innate Immune Response During Community Acquired Pneumonia
Sponsor:
University Hospital Tours
Organization:
University Hospital Tours
Study Overview
Official Title:
Innate Immunity During Community Acquired Pneumonia A Translational Approach
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
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:
ImPACT
Brief Summary:
Community acquired pneumonia CAP is a major cause of morbidity and mortality worldwide Despite recent improvement in acute management specifically for administration of antibiotics many severe presentations of pneumonia worsen progressing to Acute Respiratory Distress Syndrome ARDS a clinical entity with 40 hospital mortality
Dysregulation of immune response is thought to be largely implicated in severe pneumonia progressing to ARDS Notably experimental studies have recently suggested the implication of non-conventional T lymphocytes and innate cells in this immunopathology However no data are available in Humans in clinical settings
This study aims to explore the role of non-conventional T cells in pneumonia and ARDS in participants For this purpose 100 participants admitted to Intensive Care Unit ICU with a diagnosis of CAP will be included and 50 control participants with no pneumonia nor shock Presence and functionality of non-conventional T cells and innate cells will be explored using flow-cytometry and ex-vivo stimulation alongside with cytokines productions These analyses are conducted in the blood and for invasively ventilated participants in tracheal aspirates or broncho-alveolar fluids if available For each participants included the analyses are conducted at different time-points during ICU stay inclusion day 3 day 8 and day 15 Moreover participants with ARDS for whom a post-ICU follow-up program is normally established after discharge will have blood analysis from blood samples taken during the follow-up visit up to 8 months after inclusion
Immunophenotypage and functionality of non-conventional T cells and innate cells will be compared to clinical parameters and their evolution between CAP participants and Control participants and for each participants according to the different time-point of analysis in order to better understand dynamic of innate immunity during pneumonia and ARDS
Dysregulation of immune response is thought to be largely implicated in severe pneumonia progressing to ARDS Notably experimental studies have recently suggested the implication of non-conventional T lymphocytes and innate cells in this immunopathology However no data are available in Humans in clinical settings
This study aims to explore the role of non-conventional T cells in pneumonia and ARDS in participants For this purpose 100 participants admitted to Intensive Care Unit ICU with a diagnosis of CAP will be included and 50 control participants with no pneumonia nor shock Presence and functionality of non-conventional T cells and innate cells will be explored using flow-cytometry and ex-vivo stimulation alongside with cytokines productions These analyses are conducted in the blood and for invasively ventilated participants in tracheal aspirates or broncho-alveolar fluids if available For each participants included the analyses are conducted at different time-points during ICU stay inclusion day 3 day 8 and day 15 Moreover participants with ARDS for whom a post-ICU follow-up program is normally established after discharge will have blood analysis from blood samples taken during the follow-up visit up to 8 months after inclusion
Immunophenotypage and functionality of non-conventional T cells and innate cells will be compared to clinical parameters and their evolution between CAP participants and Control participants and for each participants according to the different time-point of analysis in order to better understand dynamic of innate immunity during pneumonia and ARDS
Detailed Description:
- Clinical and scientific background
Community acquired pneumonia is a major cause of morbidity and mortality worldwide Despite recent improvement in acute management specifically for administration of antibiotics severe pneumonia can worsen and ultimately progressing to Acute Respiratory Distress Syndrome ARDS a clinical entity with an inacceptable 40 hospital mortality From a pathophysiological point of view ARDS is characterized by a deregulation of pulmonary inflammation initially triggered by the local aggression which is in two-third of the cases a pneumonia Alteration of tissue repair is another major characteristic of this entity So far the scientific knowledge on this pathophysiology did not translate into specific therapy that could modulate efficiently the inflammatory response and to control the progression from pneumonia to ARDS andor to improve tissue repair Thus a complete reconsideration of the pathophysiological mechanisms is mandatory Recent progresses in mucosal biology and innate immunity give interesting new opportunities Specifically recently discovered unconventional T cells have shown to be major actors in shaping and modulating early immune responses in the lung mucosa during microbial aggressions and for secondary tissue repair However these evidences are limited to pre-clinical models In many other human diseases oncology immune diseases these sub-populations are already being explored as potential targets for immune therapies
- Objective of the study
The aim of this study is to explore potential implications of unconventional T cells during human severe pneumonia and ARDS
This translational study will complement experimental approaches currently undertaken in the laboratory exploring the role of unconventional T cells in murine models of severe pneumonia and ARDS
- Design
This is a prospective single-center study including participants admitted in Intensive Care Department of the university hospital of Tours for community-acquired pneumonia Given the exploratory nature of the study we designed a control group of participants admitted to ICU without evident signs of pneumonia and shock
Number of participants 300 for pneumonia group and 50 for control group
- Interventions and analysis
Blood samples will be collected at inclusion day 3 8 and 15 during patients stay in ICU For mechanically ventilated participants tracheal aspirates will be also collected at the same timing If available broncho-alveolar lavages will be also collected If ARDS or Ventilator Associated Pneumonia VAP are subsequently diagnosed supplemental blood and tracheal aspirates samples will be collected
Blood samples and airway fluid samples will be treated to perform flow cytometry analysis for immunophenotypage cellular content In some cases intra-cellular staining will be performed to assess cytokine production andor transcription factor expression Functions of unconventional T cells will also be performed after ex vivo stimulation on purified population cell sorting Cytokine level sand transcriptomic analyses will also be performed on blood samples
Clinical characteristics including respiratory parameters blood gas organ dysfunctions survival at day 28 and day 90 will also be collected Thus frequency activation status and functions of unconventional T cells will be dynamically analyzed in regard of clinical evolution within-individuals and across pneumonia vs control groups A particular focus will be made on respiratory parameters ventilation mode and for participants with ARDS PF ratio driving pressure organ dysfunctions as measured by SOFA score and microbial documentation of the pneumonia
Moreover participants treated for ARDS are usually followed in a post-ICU follow-up clinic program in the ICU where the research is conducted Thus investigators will perform analysis of the unconventional T cell compartment blood samples in the participants firstly enrolled in the study This will allow exploration of long-term imprinting on the innate immune response after the initial trigger
Community acquired pneumonia is a major cause of morbidity and mortality worldwide Despite recent improvement in acute management specifically for administration of antibiotics severe pneumonia can worsen and ultimately progressing to Acute Respiratory Distress Syndrome ARDS a clinical entity with an inacceptable 40 hospital mortality From a pathophysiological point of view ARDS is characterized by a deregulation of pulmonary inflammation initially triggered by the local aggression which is in two-third of the cases a pneumonia Alteration of tissue repair is another major characteristic of this entity So far the scientific knowledge on this pathophysiology did not translate into specific therapy that could modulate efficiently the inflammatory response and to control the progression from pneumonia to ARDS andor to improve tissue repair Thus a complete reconsideration of the pathophysiological mechanisms is mandatory Recent progresses in mucosal biology and innate immunity give interesting new opportunities Specifically recently discovered unconventional T cells have shown to be major actors in shaping and modulating early immune responses in the lung mucosa during microbial aggressions and for secondary tissue repair However these evidences are limited to pre-clinical models In many other human diseases oncology immune diseases these sub-populations are already being explored as potential targets for immune therapies
- Objective of the study
The aim of this study is to explore potential implications of unconventional T cells during human severe pneumonia and ARDS
This translational study will complement experimental approaches currently undertaken in the laboratory exploring the role of unconventional T cells in murine models of severe pneumonia and ARDS
- Design
This is a prospective single-center study including participants admitted in Intensive Care Department of the university hospital of Tours for community-acquired pneumonia Given the exploratory nature of the study we designed a control group of participants admitted to ICU without evident signs of pneumonia and shock
Number of participants 300 for pneumonia group and 50 for control group
- Interventions and analysis
Blood samples will be collected at inclusion day 3 8 and 15 during patients stay in ICU For mechanically ventilated participants tracheal aspirates will be also collected at the same timing If available broncho-alveolar lavages will be also collected If ARDS or Ventilator Associated Pneumonia VAP are subsequently diagnosed supplemental blood and tracheal aspirates samples will be collected
Blood samples and airway fluid samples will be treated to perform flow cytometry analysis for immunophenotypage cellular content In some cases intra-cellular staining will be performed to assess cytokine production andor transcription factor expression Functions of unconventional T cells will also be performed after ex vivo stimulation on purified population cell sorting Cytokine level sand transcriptomic analyses will also be performed on blood samples
Clinical characteristics including respiratory parameters blood gas organ dysfunctions survival at day 28 and day 90 will also be collected Thus frequency activation status and functions of unconventional T cells will be dynamically analyzed in regard of clinical evolution within-individuals and across pneumonia vs control groups A particular focus will be made on respiratory parameters ventilation mode and for participants with ARDS PF ratio driving pressure organ dysfunctions as measured by SOFA score and microbial documentation of the pneumonia
Moreover participants treated for ARDS are usually followed in a post-ICU follow-up clinic program in the ICU where the research is conducted Thus investigators will perform analysis of the unconventional T cell compartment blood samples in the participants firstly enrolled in the study This will allow exploration of long-term imprinting on the innate immune response after the initial trigger
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