Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT05412810 |
Other study ID # |
2018H0302 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 1, 2023 |
Est. completion date |
September 1, 2026 |
Study information
Verified date |
April 2024 |
Source |
Ohio State University |
Contact |
Sarah Karow |
Phone |
6142920031 |
Email |
sarah.karow[@]osumc.edu |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
The aim of this study is to identify and determine the levels of oxidized lipids and lipid
mediators following exposure to oxygen supplementation during mechanical ventilation by
oxidative lipidomics. The investigators will include patients with mechanical ventilation and
have received FiO2=>0.5 atleast 90 minutes and collected two sequential mini bronchoalveolar
lavage on them 24 hours apart. Mass Spectrometry Lipid chromatography will be conducted and
clinical data will be analyzed.
Description:
This proposal will elucidate an approach for precise and safe oxygenation levels and
correlation with the oxidative lipid biomarker profile of optimal oxygenation. The aim of
this study is to identify and determine the levels of oxidized lipids and lipid mediators
following exposure to oxygen supplementation during mechanical ventilation by oxidative
lipidomics. Alveolar cellular membrane and lung lining fluid are the primary targets of
therapeutic oxygen and comprised of proteins, cholesterol, and lipids. Among these
components, lipids are more susceptible to oxidation producing downstream mediators that
facilitate inflammatory and pro-fibrotic pathways. Polyunsaturated Fatty Acids (PUFAs)
account for 30% of the lipid components and contain n-3 fatty acids (i.e eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA)) and n-6 fatty acids ( arachidonic acid (AA) and
Dihomo-γ-linolenic acid (DGLA)). In the presence of reactive oxygen species and activation of
the metabolic enzymes (e.g. cyclooxygenases and lipoxyegenases), n-3 and n-6 PUFAs undergo
peroxidation to form "oxidized forms" and are further metabolized into numerous
proinflammatory and proresolving lipid mediators. Many of these lipid mediators
(Prostaglandin E2, PGE2; 11-hydroxy--eicosatetraenoic acid 11-HETE,
5-hydroxy-eicosapentaenoic acid 5-HEPE) perpetuate inflammatory mechanisms known to mediate
HALI45. Additionally, some of these mediators known as specialized proresolving mediators
(SPMs) dampen inflammation while promoting pro-resolution actions on tissue inflammation
after injury (e.g maresins, Resolvin D5). Lipidomics is one of the most sensitive approaches
for studying lipid profiles in clinical research. Given the access to lung samples
(bronchoalveoar fluid; BALF) in the setting of acute hypoxemic respiratory failure in the
ICU, this provides strong rationale to utilize this largely unexplored method to guide
clinical practice of optimal oxygenation goals.
We propose a prospective cohort study to evaluate oxidized lipid biomarkers in the BALF of
patients with acute hypoxemic respiratory failure. Inclusion criteria are 1) Adults ≥ 18
years with acute hypoxemic respiratory failure 2) with expected MV => 48 hours. Exclusion
criteria are 1) MV for procedures like EGD, bronchoscopy , colonoscopy;2) Chronic respiratory
failure prior to admission; 3) Hemoptysis, diffuse alveolar hemorrhage; 3) Primary team
prohibits bronchoscopy for a specific clinical indication or safety; 4) Medication use such
as N acetyl cysteine; aspirin, fish oil supplements. Control subjects will be those with MV
without acute hypoxemic or hypercarbic respiratory failure (e.g. MV due to stroke or
seizures). Informed consent will be taken. All consenting patients will have a two sequential
BALF collections by collected from patients on day 1 (≤6 hours of MV if initial FiO2 use is
≥0.5 for 90 minutes) and day 2 (≥48 hours after the first BALF). We have specifically chosen
these time points because Day 1 will allow us to define initial oxidized n-6 PUFA precursor
levels and their relationship to clinical outcomes. Since markers of lipid peroxidation are
at the highest on Day 2, these Day 2 samples will allow us to define the trajectory of
oxidized n-6 PUFA and associate these with clinical outcomes.
Following the BAL collection, it will be stored at -80 and Liquid chromatography-mass
spectrometry will be used for oxidative lipidomic analysis of ~130 oxidized lipid species.
Patient data will be abstracted from the chart at time of enrollment. Clinical data variables
will include: 1) demographics; 2) medical history 3) hourly FiO2 and SpO2 4) Sequential Organ
Failure Assessment (SOFA) scores for disease severity; 5) daily arterial blood gas for
PaO2/FiO2 ratio 6) daily vital signs 7) clinical laboratory studies (blood counts for
hemoglobin, electrolyte panel, lactic acid levels; 8) medications; and 9) outcomes measures
(ventilator-free days, survival). More importantly, we will note co-morbidities and treatment
related variables that may independently modify oxidized lipids and serve as confounders.
Such smoking status, active lung or breast cancer, quantity and nature of tube feeds, use of
propofol (a lipid emulsion) for sedation, and utilization of immune modulators such as
steroids, will be noted and will be adjusted for univariate and multivariate analysis.