Firstly, the study assesses the effect of bronchoalveolar lavage fluid (BAL) from patients in (acute respiratory distress syndrome (ARDS) on the life span of PNNs and on the phagocytosis of apoptotic cells by macrophages and polynuclear neutrophil (PNN).
Then, the effect of an antibody directed against "high-mobility group box 1" protein (HMGB1) and the effect of metformin on efferocytosis are studied.
Condition or disease | Intervention/treatment |
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ARDS, Human | Procedure: Bronchoalveolar lavage |
ARDS (acute respiratory distress syndrome) is a syndrome that causes significant mortality and morbidity. This syndrome is characterized by an alveolitis with polynuclear neutrophil (PNN). PNNs play an important role in the persistence and in injuries induced by ARDS. Several animal studies have shown that lesional edema can be increased by two important mechanisms: the increase in the lifespan of PNNs in the lung and the decrease in the phagocytosis capacities of apoptotic cells (efferocytosis) by macrophages and PNNs.
However, confirmation of these data in humans does not exist, and knowledge of the mechanisms that may increase lung damage during ARDS will limit it and thus reduce the mechanical ventilation time of these patients as well as the mortality associated with ARDS.
" high-mobility group box 1 " (HMGB1) protein may be involved in reducing efferocytosis capacity. Similarly, activation of AMP-activated protein kinase (AMPk) could restore the clearance capacity of apoptotic cells in macrophages and PNNs.
Study Type : | Observational |
Actual Enrollment : | 42 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System |
Actual Study Start Date : | May 5, 2015 |
Actual Primary Completion Date : | May 5, 2016 |
Actual Study Completion Date : | May 5, 2016 |
Group/Cohort | Intervention/treatment |
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ARDS group
Inpatients hospitalized in medical intensive care with a table of ARDS defined according to the Berlin criteria and requiring an BAL for a diagnostic purpose under a suspicion of pneumopathy acquired under mechanical ventilation.
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Procedure: Bronchoalveolar lavage |
Control group
The control group will be made up of patients with an BAL considered normal (endoscopy patients from the pneumology department). The normality of the BAL is defined by a normocellular wash with cellularity: < 150,000 to 200,000 cells/mL Cell composition (formula): macrophages: 80-90%, lymphocytes 5 to 10% (< 20%), neutrophils: < 5%, eosinophils: < 2%.
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Procedure: Bronchoalveolar lavage |
The lifespan of the PNNs is an indicator of apoptosis : two groups are compared with and without incubation in BAL fluid.
Neutrophil necrosis was assessed by flow cytometry using a phycoerythrin-conjugated active caspase-3 apoptosis kit (Becton Dickinson, USA)
This index relates the ability of the PNNs to produce neutrophil extracellular traps (NETs).
The release of NETs was quantified by measuring fluorescence with a microplate fluorescence reader (Varioskan, ThermoFisher Scientific, USA).
Ages Eligible for Study: | Child, Adult, Older Adult |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
Exclusion Criteria:
France | |
CHU de Rennes | |
Rennes, France, 35033 |
Principal Investigator: | Jean-Marc TADIE, MD, PhD | University Hospital of Rennes |
Tracking Information | |||||
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First Submitted Date | July 2, 2019 | ||||
First Posted Date | July 5, 2019 | ||||
Last Update Posted Date | July 8, 2019 | ||||
Actual Study Start Date | May 5, 2015 | ||||
Actual Primary Completion Date | May 5, 2016 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
Lifespan of the PNNs [ Time Frame: 24 hours after BAL ] The lifespan of the PNNs is an indicator of apoptosis : two groups are compared with and without incubation in BAL fluid.
Neutrophil necrosis was assessed by flow cytometry using a phycoerythrin-conjugated active caspase-3 apoptosis kit (Becton Dickinson, USA)
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Original Primary Outcome Measures | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures |
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Original Secondary Outcome Measures | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System | ||||
Official Title | Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System | ||||
Brief Summary |
Firstly, the study assesses the effect of bronchoalveolar lavage fluid (BAL) from patients in (acute respiratory distress syndrome (ARDS) on the life span of PNNs and on the phagocytosis of apoptotic cells by macrophages and polynuclear neutrophil (PNN). Then, the effect of an antibody directed against "high-mobility group box 1" protein (HMGB1) and the effect of metformin on efferocytosis are studied. |
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Detailed Description |
ARDS (acute respiratory distress syndrome) is a syndrome that causes significant mortality and morbidity. This syndrome is characterized by an alveolitis with polynuclear neutrophil (PNN). PNNs play an important role in the persistence and in injuries induced by ARDS. Several animal studies have shown that lesional edema can be increased by two important mechanisms: the increase in the lifespan of PNNs in the lung and the decrease in the phagocytosis capacities of apoptotic cells (efferocytosis) by macrophages and PNNs. However, confirmation of these data in humans does not exist, and knowledge of the mechanisms that may increase lung damage during ARDS will limit it and thus reduce the mechanical ventilation time of these patients as well as the mortality associated with ARDS. " high-mobility group box 1 " (HMGB1) protein may be involved in reducing efferocytosis capacity. Similarly, activation of AMP-activated protein kinase (AMPk) could restore the clearance capacity of apoptotic cells in macrophages and PNNs. |
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Study Type | Observational | ||||
Study Design | Observational Model: Cohort Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||
Biospecimen | Not Provided | ||||
Sampling Method | Non-Probability Sample | ||||
Study Population |
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Condition | ARDS, Human | ||||
Intervention | Procedure: Bronchoalveolar lavage | ||||
Study Groups/Cohorts |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Completed | ||||
Actual Enrollment |
42 | ||||
Original Actual Enrollment | Same as current | ||||
Actual Study Completion Date | May 5, 2016 | ||||
Actual Primary Completion Date | May 5, 2016 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender | Not Provided | ||||
Ages | Child, Adult, Older Adult | ||||
Accepts Healthy Volunteers | Not Provided | ||||
Contacts | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT04008225 | ||||
Other Study ID Numbers | 35RC15_9885 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Responsible Party | Rennes University Hospital | ||||
Study Sponsor | Rennes University Hospital | ||||
Collaborators | Not Provided | ||||
Investigators |
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PRS Account | Rennes University Hospital | ||||
Verification Date | July 2019 |