Clinical trial NCT05414370: Hyperoxia Induced Pulmonary Inflammation and Organ Injury: a Human in Vivo Model
Official title: Effects of Hyperoxia Induced Pulmonary Inflammation and Organ Injury in a Human in Vivo Model
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Oxygen Toxicity
Pulmonary Injury
Acute Lung Injury
Lead sponsor: Belfast Health and Social Care Trust
Sponsor class: OTHER
First posted: 2022-06-10
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Oxygen is the most commonly administered therapy in critical illness. Accumulating evidence suggests that patients often achieve supra-physiological levels of oxygenation in the critical care environment. Furthermore, hyperoxia related complications following cardiac arrest, myocardial infarction and stroke have also been reported. The underlying mechanisms of hyperoxia mediated injury remain poorly understood and there are currently no human in vivo studies exploring the relationship between hyperoxia and direct pulmonary injury and inflammation as well as distant organ injury.

The current trial is a mechanistic study designed to evaluate the effects of prolonged administration of high-flow oxygen (hyperoxia) on pulmonary and systemic inflammation. The study is a randomised, double-blind, placebo-controlled trial of high-flow nasal oxygen therapy versus matching placebo (synthetic medical air). We will also incorporate a model of acute lung injury induced by inhaled endotoxin (LPS) in healthy human volunteers. Healthy volunteers will undergo bronchoalveolar lavage (BAL) at 6 hours post-intervention to enable measurement of pulmonary and systemic markers of inflammation, oxidative stress and cellular injury.


Eligibility criteria: Inclusion Criteria:

1. Healthy non-smoking subjects less than 45 years of age and BMI \< 29 kg/m²

Exclusion Criteria:

1. Age \< 18 years
2. On concomitant medications including over the counter medications excluding oral contraception and paracetamol
3. Previous adverse reactions to LPS, lignocaine or sedative agents
4. Pregnant or Breast-Feeding
5. Participation in a clinical trial of an investigational medicinal product within 30 days
6. Consent declined
7. History of asthma or other respiratory conditions
8. Smoking/ e cigarette use
9. Marijuana use or other inhaled products with or without nicotine in the last 3 months
10. Alcohol abuse, as defined by the Alcohol Use Disorders Identification Test (AUDIT)
11. Subjects with history of prior conventional cigarette (\> 100 cigarettes lifetime and smoking within 6 months) or electronic cigarette use.

Primary outcomes:
measure: Bronchoalveolar lavage Interleukin-8 (IL-8) concentration
timeFrame: 6 hours post-intervention
Secondary outcomes:
measure: Bronchoalveolar lavage cytokines including but not limited to tumour necrosis factor alpha, IL-1 beta and IL-6
timeFrame: 6 hours post-intervention
measure: Bronchoalveolar lavage proteases and anti-proteases including but not limited to Matrix Metalloproteinases (MMP-2, MMP-8, MMP-9 and MMP-11), Tissue Inhibitors of Metalloproteinase (TIMPs 1-2) and neutrophil elastase
timeFrame: 6 hours post-intervention
measure: Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes)
timeFrame: 6 hours post-intervention
measure: Plasma cytokines including but not limited to IL-8, tumour necrosis factor alpha, IL-1 beta and IL-6
timeFrame: 6 and 24 hours post-intervention
measure: Bronchoalveolar lavage soluble programmed cell death receptor (SP-D)
timeFrame: 6 hours post-intervention
measure: Bronchoalveolar lavage total protein
timeFrame: 6 hours post-intervention
measure: Bronchoalveolar lavage receptor for advanced glycation end-products (RAGE)
timeFrame: 6 hours post-intervention
measure: Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE)
timeFrame: 6 hours post-intervention
measure: Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL)
timeFrame: 6 hours post-intervention
measure: Plasma advanced glycation end products (AGE)
timeFrame: 6 and 24 hours post-intervention
measure: Plasma oxidised low density lipoprotein (oxLDL)
timeFrame: 6 and 24 hours post-intervention
measure: Plasma 4-hydroxy-2-nonenal (4-HNE)
timeFrame: 6 and 24 hours post-intervention
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trus
Study officials:
affiliation: Queen's University, Belfast
name: Danny McAuley, MD
role: PRINCIPAL_INVESTIGATOR
References: