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

Sponsor
Belfast Health and Social Care Trust (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05414370
Collaborator
(none)
53
1
2
16
3.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Liquid oxygen
  • Drug: medical air
N/A

Study Design

Study Type:
Interventional
Anticipated Enrollment :
53 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Effects of Hyperoxia Induced Pulmonary Inflammation and Organ Injury in a Human in Vivo Model
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Liquid medical oxygen

Liquid medical oxygen will be administered using high-flow nasal cannula delivery system.

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.
Other Names:
  • Liquid medical oxygen
  • Placebo Comparator: Synthetic medical air

    Synthetic medical air will be administered using high-flow nasal cannula delivery system.

    Drug: 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.
    Other Names:
  • Synthetic medical air
  • Outcome Measures

    Primary Outcome Measures

    1. Bronchoalveolar lavage Interleukin-8 concentration [6 hours post-intervention]

      To determine the effects of hyperoxia on alveolar inflammatory response

    Secondary Outcome Measures

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. Bronchoalveolar lavage total protein [6 hours post-intervention]

      To determine the effects of hyperoxia on alveolar epithelial and endothelial function

    7. 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

    8. Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE) [6 hours post-intervention]

      To determine the effects of hyperoxia on oxidative stress

    9. Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL) [6 hours post-intervention]

      To determine the effects of hyperoxia on oxidative stress

    10. Plasma advanced glycation end products (AGE) [6 and 24 hours post-intervention]

      To determine the effects of hyperoxia on oxidative stress

    11. Plasma oxidised low density lipoprotein (oxLDL) [6 and 24 hours post-intervention]

      To determine the effects of hyperoxia on oxidative stress

    12. Plasma 4-hydroxy-2-nonenal (4-HNE) [6 and 24 hours post-intervention]

      To determine the effects of hyperoxia on oxidative stress

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Belfast Health and Social Care Trus Belfast United Kingdom

    Sponsors and Collaborators

    • Belfast Health and Social Care Trust

    Investigators

    • Principal Investigator: Danny McAuley, MD, Queen's University, Belfast

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Belfast Health and Social Care Trust
    ClinicalTrials.gov Identifier:
    NCT05414370
    Other Study ID Numbers:
    • 18129MS-AS
    First Posted:
    Jun 10, 2022
    Last Update Posted:
    Jul 25, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 25, 2022