Soluble Forms and Ligands of RAGE in ALI/ARDS (SoLiRAGE).

This study has been completed.
Sponsor:
Collaborators:
Faculté de Médecine Clermont-Ferrand, Université Clermont I
Pôle de Recherche et d'Enseignement Supérieur (PRES) Clermont Université
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier:
NCT01270295
First received: January 4, 2011
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

RAGE, the receptor for advanced glycation end products, is a novel marker of alveolar epithelial type I cell injury. Soluble RAGE (sRAGE) is elevated in the plasma and in the pulmonary edema fluid from patients with ALI/ARDS, but one should acknowledge that the RAGE/NF-B axis is also involved in the pathophysiology of various other conditions. Few data are available about the levels of soluble forms and ligands of RAGE in the setting of ALI/ARDS. The purpose of this observational prospective study is to describe soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in ICU patients with ALI/ARDS.


Condition
Acute Lung Injury
Acute Respiratory Distress Syndrome
Mechanical Ventilation

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: Soluble Forms and Ligands of the Receptor for Advanced Glycation End Products (RAGE) in the Pulmonary Edema Fluid and Plasma From ICU Patients With ALI/ARDS : an Observational Prospective Study.

Resource links provided by NLM:


Further study details as provided by University Hospital, Clermont-Ferrand:

Primary Outcome Measures:
  • Soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in the plasma from ICU patients within the first 24 hours after onset of ALI/ARDS [ Time Frame: within the first 24 hours after onset of ALI/ARDS ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To describe kinetics of evolution of soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in ICU patients with or without ALI/ARDS: biomarkers levels in pulmonary edema fluid and plasma on day 1, day 3, and day 6 [ Time Frame: on day 1, day 3, and day 6 ] [ Designated as safety issue: Yes ]
  • To describe the plasma and pulmonary levels of soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) in the setting of ALI/ARDS. [ Time Frame: on day 1, day 3, and day 6. ] [ Designated as safety issue: Yes ]
  • To test the correlation between soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels and net alveolar fluid clearance in patients within the first 24 hours after onset of ALI/ARDS. [ Time Frame: within the first 24 hours after onset of ALI/ARDS ] [ Designated as safety issue: Yes ]
  • To decribe venous-to-arterial differences in soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels during ALI/ARDS. - [ Time Frame: on day 1, day 3, and day 6. ] [ Designated as safety issue: Yes ]
  • To test the correlation between biomarkers levels (soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs)) and CT-scan lung morphology in patients within the first 24 hours after onset of ALI/ARDS [ Time Frame: within the first 24 hours after onset of ALI/ARDS ] [ Designated as safety issue: Yes ]
  • To describe soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in ICU patients under mechanical ventilation (MV), in order to assess the influence of MV on these markers: biomarkers levels in pulmonary edema fluid and plasma [ Time Frame: on day 1, day 3, and day 6 ] [ Designated as safety issue: Yes ]
  • To test the prognostic value of soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in ICU patients with ALI/ARDS: [ Time Frame: on day 28 ] [ Designated as safety issue: Yes ]
  • To test the correlation between biomarkers levels (soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, [ Time Frame: on day 1, day 3, and day 6. ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: January 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

The receptor for advanced glycation end products (RAGE) is now identified as a 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. While the precise function of RAGE remains unclear, the elevated levels of RAGE, and its soluble isoform sRAGE, correlate with severity of ALI/ARDS in human and animal studies, and RAGE levels could reflect impaired alveolar fluid clearance. Frequently, the biology of RAGE coincides with settings in which ligands of the receptor accumulate, especially in a proinflammatory environment. More work is needed for us to understand the mechanisms by which RAGE is regulated during ALI/ARDS, especially with regard to the expression of its soluble forms and the involvement of its potential ligands.

DESIGN NARRATIVE:

This observational prospective clinical study will describe and compare soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in the alveolar edema fluid and in the plasma from ICU patients enrolled within the first 24 hours after onset of ALI/ARDS, and from patients under mechanical ventilation (control group).

Edema fluid and plasma samples will be collected simultaneously on day 1, day 3 and day 6, in order to describe kinetics of evolution of soluble forms and ligands of RAGE levels. Undiluted pulmonary edema fluid samples will be collected in intubated patients only, and blood samples will be simultaneously gathered from indwelling arterial and central venous catheters. The concentrations of soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) will be measured in duplicate by ELISA.

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Defined population

Criteria

Inclusion Criteria:

  • ICU patients under mechanical ventilation
  • Patients within the first 24 hours after onset of ALI/ARDS according to the 1994 American-European Consensus Conference (AECC)

Exclusion Criteria:

  • Pregnancy
  • Acute exacerbation of diabetes
  • Dialysis for end-stage kidney disease
  • Alzheimer's disease
  • Amyloidosis
  • Evolutive neoplastic lesion
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01270295

Locations
France
CHU Clermont-Ferrand
Clermont-Ferrand, France, 63003
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Faculté de Médecine Clermont-Ferrand, Université Clermont I
Pôle de Recherche et d'Enseignement Supérieur (PRES) Clermont Université
  More Information

No publications provided

Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT01270295     History of Changes
Other Study ID Numbers: CHU-0086
Study First Received: January 4, 2011
Last Updated: March 12, 2013
Health Authority: France: Ministry of Health

Keywords provided by University Hospital, Clermont-Ferrand:
Receptor for advanced glycation end products (RAGE)
Soluble RAGE (sRAGE)
Endogenous secretory RAGE (esRAGE)
High-mobility group box-1 protein (HMGB-1)
Extracellular newly-identified RAGE-binding protein (EN-RAGE or S100A12)
Advanced glycation endproducts (AGEs)
Pentosidine
N--carboxymethyllysine
Acute lung injury (ALI)
Acute respiratory distress syndrome (ARDS)
Alveolar epithelium
Mechanical ventilation
Intensive Care Unit (ICU)

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Wounds and Injuries
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries

ClinicalTrials.gov processed this record on July 22, 2014