NCT02545621

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Sep 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2015

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

September 8, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 10, 2015

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2016

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

May 12, 2020

Status Verified

July 1, 2016

Enrollment Period

1 year

First QC Date

September 8, 2015

Last Update Submit

May 9, 2020

Conditions

Acute Respiratory Distress SyndromeMechanical Ventilation

Keywords

Receptor for advanced glycation end products (RAGE)Acute respiratory distress syndrome (ARDS)Monocyte/Macrophage activationFluorescence-Activated Cell Sorting (FACS) analysisThioredoxin interacting protein (TXNIP)NOD-like receptor family, pyrin domain containing 3 (NLRP3)Inflammasome

Outcome Measures

Primary Outcomes (1)

  • FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages

    FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages from patients within the first 24 hours after onset of ARDS (ARDS group) and from sex- and age-matched mechanically ventilated controls (control group)

    at day1

Secondary Outcomes (2)

  • - FACS analysis of M1 ("pro-inflammatory") and M2 ("anti-inflammatory") markers

    at baseline

  • IL-1β, TXNIP, NLRP3, sRAGE, HMGB1, S100A12 measurements

    at baseline

Study Arms (2)

ARDS Group (acute respiratory distress syndrome)

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

Other: RAGE TXNIP Inflammasome axis

control group

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

Other: RAGE TXNIP Inflammasome axis

Interventions

RAGE TXNIP Inflammasome axisOTHER
ARDS Group (acute respiratory distress syndrome)control group

Eligibility Criteria

Age18 Years - 95 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

ICU patients without ARDS and under mechanical ventilation for less than 24 hours

You may qualify if:

  • ICU patients without ARDS and under mechanical ventilation for less than 24 hours
  • Patients within the first 24 hours after onset of moderate to severe ARDS according to the 2012 Berlin definition (ARDS group)

You may not qualify if:

  • \- Pregnancy
  • Acute exacerbation of diabetes (ketoacidosis, hyperosmolar hyperglycemic state)
  • Patient under mechanical ventilation for \> 7 days
  • Dialysis-dependent chronic renal failure
  • Alzheimer's disease
  • Amyloidosis
  • Evolutive neoplastic lesion
  • Chronic pulmonary disease requiring long-term oxygen therapy or mechanical ventilation
  • Chemotherapy treatment in the last 30 days
  • Severe neutropenia (\<0.5 G/l)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration Disorders

Study Officials

  • Mathieu JABAUDON

    University Hospital, Clermont-Ferrand

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 8, 2015

First Posted

September 10, 2015

Study Start

September 1, 2015

Primary Completion

September 1, 2016

Study Completion

October 1, 2016

Last Updated

May 12, 2020

Record last verified: 2016-07

Locations

FR(1)