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

Acute Lung Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05414370
• Other study ID #: 18129MS-AS
• Status: Recruiting
• Phase: N/A
• Start date: December 2, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: January 2024
• Source: Belfast Health and Social Care Trust
• Contact: Danny McAuley, MD
• Phone: +442890 972144
• Email: d.f.mcauley[@]qub.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Hyperoxia
• Inflammation
• Lung Injury
• Oxygen Toxicity
• Pneumonia
• Pulmonary Injury
• Wounds and Injuries

Intervention

Drug:
• Liquid oxygen
Liquid medical oxygen will be administered for 6 hours using high-flow nasal cannula delivery system with an Fi02 of 100% and flow rate of 60 litres per minute.
• medical air
Synthetic medical air will be administered for 6 hours using high-flow nasal cannula delivery system with a flow rate of 60 litres per minute.

Locations

Country	Name	City	State
United Kingdom	Belfast Health and Social Care Trus	Belfast

Sponsors (1)

Lead Sponsor	Collaborator
Belfast Health and Social Care Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

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