Clinical Trials Logo
  1. Home
  2. Mechanical Ventilation
  3. NCT02545621

A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study

Acute Respiratory Distress Syndrome Clinical Trial

Official title:
A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study

Clinical Trial Summary

RAGE (the receptor for advanced glycation end-products) is a marker of alveolar type I cell injury and a pivotal mediator of acute inflammation and innate immunity. RAGE pathway is highly regulated; the interaction of the transmembrane receptor with its various ligands (e.g. HMGB1, S100A12) ultimately leads to NF-kB activation and RAGE upregulation itself, but precise RAGE functions and intracellular pathways remain underexplored. During ARDS, monocyte and macrophage activation could modulate alveolar inflammation and repair.

As RAGE is also expressed at the surface of monocytes/macrophages, we hypothesize that alveolar monocyte/macrophage activation may be mediated through a RAGE-TXNIP (thioredoxin interacting protein)-NLRP3/inflammasome intracellular pathway. The purpose of this observational prospective study is to compare alveolar monocyte/macrophage activation profiles (as assessed by Fluorescence-Activated Cell Sorting (FACS)) in mechanically ventilated patients with or without ARDS.

Clinical Trial Description

BACKGROUND:

The receptor for advanced glycation end products (RAGE) was recently identified as a promising new marker of alveolar type I cell injury. RAGE is a member of the immunoglobulin superfamily that acts as a multiligand receptor and is involved in propagating inflammatory responses in various cell populations. While the precise function of RAGE remains unclear, the elevated levels of RAGE, and its soluble isoform sRAGE, correlate with severity of acute respiratory distress syndrome (ARDS) in human and animal studies.

RAGE pathway is highly regulated; the interaction of the transmembrane receptor with its various ligands (e.g. HMGB1, S100A12) ultimately leads to NF-kB activation and RAGE upregulation itself. During ARDS, monocyte and macrophage activation could modulate alveolar inflammation and repair. As RAGE is also expressed at the surface of monocytes/macrophages, we hypothesize that alveolar monocyte/macrophage activation may be mediated through a RAGE-TXNIP (thioredoxin interacting protein)-NLRP3/inflammasome intracellular pathway.

DESIGN NARRATIVE:

The purpose of this monocentric observational prospective pathophysiology study is to compare alveolar monocyte/macrophage activation profiles between patients with or without ARDS.

Using Fluorescence-Activated Cell Sorting (FACS) analysis, monocyte/macrophage activation profiles will be characterized in patients within the first 24 hours after onset of ARDS and in matched mechanically ventilated controls. Markers of M1 ("pro-inflammatory") or M2 ("anti-inflammatory") activation, along with RAGE, TXNIP, NLRP3 FACS labeling in alveolar monocytes/macrophages will be analyzed along with protein measurements (IL-1β, TXNIP, NLRP3, sRAGE, HMGB1, S100A12) in the bronchoalveolar lavage fluid. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details
NCT number NCT02545621
Study type Observational
Source University Hospital, Clermont-Ferrand
Contact
Status Completed
Phase
Start date September 2015
Completion date October 2016
View Details
See also
  Status Clinical Trial Phase
Completed NCT04384445 - Zofin (Organicell Flow) for Patients With COVID-19 Phase 1/Phase 2
Recruiting NCT05535543 - Change in the Phase III Slope of the Volumetric Capnography by Prone Positioning in Acute Respiratory Distress Syndrome
Completed NCT04695392 - Restore Resilience in Critically Ill Children N/A
Terminated NCT04972318 - Two Different Ventilatory Strategies in Acute Respiratory Distress Syndrome Due to Community-acquired Pneumonia N/A
Completed NCT04534569 - Expert Panel Statement for the Respiratory Management of COVID-19 Related Acute Respiratory Failure (C-ARF)
Completed NCT04078984 - Driving Pressure as a Predictor of Mechanical Ventilation Weaning Time on Post-ARDS Patients in Pressure Support Ventilation.
Completed NCT04451291 - Study of Decidual Stromal Cells to Treat COVID-19 Respiratory Failure N/A
Not yet recruiting NCT06254313 - The Role of Cxcr4Hi neutrOPhils in InflueNza
Not yet recruiting NCT04798716 - The Use of Exosomes for the Treatment of Acute Respiratory Distress Syndrome or Novel Coronavirus Pneumonia Caused by COVID-19 Phase 1/Phase 2
Withdrawn NCT04909879 - Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells for Non-COVID-19 Acute Respiratory Distress Syndrome Phase 2
Not yet recruiting NCT02881385 - Effects on Respiratory Patterns and Patient-ventilator Synchrony Using Pressure Support Ventilation N/A
Terminated NCT02867228 - Noninvasive Estimation of Work of Breathing N/A
Completed NCT02232841 - Electrical Impedance Imaging of Patients on Mechanical Ventilation N/A
Withdrawn NCT02253667 - Palliative Use of High-flow Oxygen Nasal Cannula in End-of-life Lung Disease Patients N/A
Completed NCT02889770 - Dead Space Monitoring With Volumetric Capnography in ARDS Patients N/A
Completed NCT01504893 - Very Low Tidal Volume vs Conventional Ventilatory Strategy for One-lung Ventilation in Thoracic Anesthesia N/A
Withdrawn NCT01927237 - Pulmonary Vascular Effects of Respiratory Rate & Carbon Dioxide N/A
Completed NCT02814994 - Respiratory System Compliance Guided VT in Moderate to Severe ARDS Patients N/A
Completed NCT01680783 - Non-Invasive Ventilation Via a Helmet Device for Patients Respiratory Failure N/A
Completed NCT02214576 - High Flow Nasal Canula Oxygen Helps Preoxygenate ARDS Patients N/A