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

NCT05414370 | Unknown DMC

• 1 other identifier: 18129MS-AS
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Oxygen Toxicity; Pulmonary Injury; Acute Lung Injury

Outcome Measures

Primary Outcomes (1)

• Bronchoalveolar lavage Interleukin-8 (IL-8) concentration

  To determine the effects of hyperoxia on alveolar inflammatory response

  6 hours post-intervention

Secondary Outcomes (12)

• Bronchoalveolar lavage cytokines including but not limited to tumour necrosis factor alpha, IL-1 beta and IL-6

  6 hours post-intervention

• 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

• Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes)

  6 hours post-intervention

• 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

• Bronchoalveolar lavage soluble programmed cell death receptor (SP-D)

  6 hours post-intervention

Study Arms (2)

Liquid medical oxygen

ACTIVE COMPARATOR

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

Drug: Liquid oxygen

Synthetic medical air

PLACEBO COMPARATOR

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

Drug: medical air

Interventions

Liquid oxygen DRUG

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.

Also known as: Liquid medical oxygen

Liquid medical oxygen

medical air DRUG

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.

Also known as: Synthetic medical air

Synthetic medical air

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Belfast Health and Social Care Trust: lead

Study Sites (1)

Belfast Health and Social Care Trus

Belfast, United Kingdom

RECRUITING

Related Publications (1)

• Linden D, Dorrian D, Tandel S, McKelvey M, Bailey M, Conlon J, Moore D, Carr S, Taggart CC, Bradley JM, Kidney J, OKane CM, McAuley DF. Effects of Hyperoxia on Pulmonary Inflammation and organ injury in a human in vivo model (HIPI): study protocol of a randomised, double-blind, placebo-controlled trial. BMJ Open Respir Res. 2025 Feb 12;12(1):e002393. doi: 10.1136/bmjresp-2024-002393.

  PMID: 39939102 DERIVED

MeSH Terms

Conditions

Lung Injury; Acute Lung Injury

Interventions

Air

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Thoracic Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Danny McAuley, MD

  Queen's University, Belfast

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danny McAuley, MD

CONTACT

+442890 972144; d.f.mcauley@qub.ac.uk

Dermot Linden, PhD

CONTACT

07812008626; dlinden02@qub.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: June 10, 2022
• Study Start: December 2, 2022
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: January 29, 2024

Record last verified: 2024-01

Locations

GB (1)