Hyperoxia Induced Pulmonary Inflammation and Organ Injury: a Human in Vivo Model

Not Applicable

Recruiting

• Conditions: Pulmonary Injury; Acute Lung Injury; Oxygen Toxicity
• Interventions: Drug: Liquid oxygen; Drug: medical air

• Registration Number: NCT05414370
• Lead Sponsor: Belfast Health and Social Care Trust

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-11
• Study First Submitted QC: 2022-06-08
• Study First Posted: 2022-06-10
• Study Start: 2022-12-02
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-26
• Last Update Posted: 2024-01-29
• Primary Completion: 2024-12-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 53

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liquid medical oxygen	Liquid oxygen	Liquid medical oxygen will be administered using high-flow nasal cannula delivery system.
Synthetic medical air	medical air	Synthetic medical air will be administered using high-flow nasal cannula delivery system.

Primary Outcome Measures

Name	Time	Method
Bronchoalveolar lavage Interleukin-8 (IL-8) concentration	6 hours post-intervention	To determine the effects of hyperoxia on alveolar inflammatory response

Secondary Outcome Measures

Name	Time	Method
Bronchoalveolar lavage cytokines including but not limited to tumour necrosis factor alpha, IL-1 beta and IL-6	6 hours post-intervention	To determine the effects of hyperoxia on alveolar inflammatory response biomarkers
Bronchoalveolar lavage total protein	6 hours post-intervention	To determine the effects of hyperoxia on alveolar epithelial and endothelial function
Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE)	6 hours post-intervention	To determine the effects of hyperoxia on oxidative stress
Plasma advanced glycation end products (AGE)	6 and 24 hours post-intervention	To determine the effects of hyperoxia on oxidative stress
Plasma oxidised low density lipoprotein (oxLDL)	6 and 24 hours post-intervention	To determine the effects of hyperoxia on oxidative stress
Plasma 4-hydroxy-2-nonenal (4-HNE)	6 and 24 hours post-intervention	To determine the effects of hyperoxia on oxidative stress
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	6 hours post-intervention	To determine the effects of hyperoxia on alveolar protease and antiprotease activity
Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes)	6 hours post-intervention	To determine the effects of hyperoxia on alveolar cell populations
Bronchoalveolar lavage soluble programmed cell death receptor (SP-D)	6 hours post-intervention	To determine the effects of hyperoxia on alveolar epithelial and endothelial function
Plasma cytokines including but not limited to IL-8, tumour necrosis factor alpha, IL-1 beta and IL-6	6 and 24 hours post-intervention	To determine the effects of hyperoxia on plasma inflammatory response biomarkers
Bronchoalveolar lavage receptor for advanced glycation end-products (RAGE)	6 hours post-intervention	To determine the effects of hyperoxia on alveolar epithelial and endothelial function
Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL)	6 hours post-intervention	To determine the effects of hyperoxia on oxidative stress

Trial Locations

Locations (1)

Belfast Health and Social Care Trus; 🇬🇧 Belfast, United Kingdom