Skip to main content
OpenTrials
Completed

NCT Number: NCT04008225

Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System

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.

Completed

Looking for future studies?

Notify Me

Key information

Study type

Observational

Primary location

CHU de Rennes

Rennes, 35033, France

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ARDS Group : Inpatients hospitalized in medical intensive care with an ARDS defined according to the Berlin criteria and requiring an BAL(for diagnostic purpose in suspicion of pneumopathy acquired under mechanical ventilation).
  • Control group : The control population is made up with patients with a 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%.

Exclusion criteria

  • Age < 18 years;
  • Pregnant women ;
  • Persons deprived of their liberty by judicial or administrative decision;
  • Persons legally incapable;
  • Persons not affiliated to a social security system;
  • Previously immunocompromised patients (HIV infection, hematopathy, organ transplantation, immunosuppression);
  • Patients who do not require a lung sample.

Treatment and study plan

Bronchoalveolar lavage

Procedure

Primary outcomes

  1. 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)

Secondary outcomes

  1. PNNs phagocytic index

    Time frame: 24 hours after BAL

    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).

  2. Efferocytosis index

    Time frame: 24 hours after BAL

    The efferocytosis index was determined on 300 cells as the percentage of Human monocyte-derived macrophages (HMDMs) containing at least one ingested apoptotic neutrophil.

  3. Increase of PNNs phagocytic index with HMGB1 activator

    Time frame: 24 hours after BAL

    PNNs phagocytic index is measured after incubation with an anti-HMGB1 neutralising antibody

  4. Increase of Efferocytosis index metformin

    Time frame: 24 hours after BAL

    efferocytosis index was determined after incubation with an AMP-activated protein kinase (AMPK) activator (metformin)

Sponsors and collaborators

Lead sponsor

Rennes University Hospital

Other

Registry information

Acronym: BALARDS

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Jul 5, 2019
Registry last updated
Jul 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.