Acute Respiratory Distress SyndromeNCT02545621
A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study
An observational study of Acute Respiratory Distress Syndrome and Mechanical Ventilation, run by University Hospital, Clermont-Ferrand at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Mechanical Ventilation
- What is being tested?
- RAGE TXNIP Inflammasome axis
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2015to Oct 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: ICU patients without ARDS and under mechanical ventilation for less than 24 hours
Who may be able to join
- 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)
Who cannot join
- - 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
Show all 10Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Being tested
- RAGE TXNIP Inflammasome axis
- Keywords
- Receptor for advanced glycation end products (RAGE), Acute respiratory distress syndrome (ARDS), Monocyte/Macrophage activation, Fluorescence-Activated Cell Sorting (FACS) analysis, Thioredoxin interacting protein (TXNIP), NOD-like receptor family, pyrin domain containing 3 (NLRP3), Inflammasome
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAGE TXNIP Inflammasome axisOther
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: RAGE TXNIP Inflammasome axis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: at day1
Secondary outcomes (2)
- FACS analysis of M1 ("pro-inflammatory") and M2 ("anti-inflammatory") markers
- FACS analysis of M1 ("pro-inflammatory") and M2 ("anti-inflammatory") markers (e.g., CD45, CD16, CD14, CD163, CD206, ICAM-1) in alveolar monocytes/macrophages from patients from both groups at baseline
Measured: at baseline
IL-1β, TXNIP, NLRP3, sRAGE, HMGB1, S100A12 measurements
- IL-1β, TXNIP, NLRP3, sRAGE, HMGB1, S100A12 measurements (duplicate ELISA) in the bronchoalveolar lavage fluid from patients from both groups at baseline
Measured: at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2015 (estimated)
- Study startSep 2015
- Primary completionSep 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mathieu JABAUDON, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02545621
- Sponsor's protocol ID
- CHU-0243
- Status last verified
- Jul 2016
- First submitted
- 8 Sep 2015
- Last updated
- 12 May 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study
- ClinicalTrials.gov ID
- NCT02545621
- Acronym / sponsor ID
- CHU-0243
- Keywords
- Receptor for advanced glycation end products (RAGE), Acute respiratory distress syndrome (ARDS), Monocyte/Macrophage activation, Fluorescence-Activated Cell Sorting (FACS) analysis, Thioredoxin interacting protein (TXNIP), NOD-like receptor family, pyrin domain containing 3 (NLRP3), Inflammasome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- Sep 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 10 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARDS Group (acute respiratory distress syndrome) | – | Other: RAGE TXNIP Inflammasome axisThe purpose of this monocentric observational prospective pathophysiology study is to compare alveolar monocyte/macrophage activation profiles between patients with or without ARDS |
| control group | – | Other: RAGE TXNIP Inflammasome axisThe purpose of this monocentric observational prospective pathophysiology study is to compare alveolar monocyte/macrophage activation profiles between patients with or without ARDS |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- ICU patients without ARDS and under mechanical ventilation for less than 24 hours
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (10 listed)
- - Pregnancy
- Acute exacerbation of diabetes (ketoacidosis, hyperosmolar hyperglycemic state)
- Patient under mechanical ventilation for > 7 days
- Dialysis-dependent chronic renal failure
- Alzheimer's disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAGE TXNIP Inflammasome axis | Other | ARDS Group (acute respiratory distress syndrome), control group |
Primary outcome
FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages
Time frame: at day1
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)
2 secondary outcomes
- FACS analysis of M1 ("pro-inflammatory") and M2 ("anti-inflammatory") markers
Time frame: at baseline
IL-1β, TXNIP, NLRP3, sRAGE, HMGB1, S100A12 measurements
Time frame: at baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mathieu JABAUDON principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome and Mechanical Ventilation, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages (time frame: at day1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2020.