Oxygen ToxicityNCT05414370
Hyperoxia Induced Pulmonary Inflammation and Organ Injury: a Human in Vivo Model
A study testing Liquid oxygen and medical air in people with Oxygen Toxicity and Pulmonary Injury, run by Belfast Health and Social Care Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Oxygen Toxicity, Pulmonary Injury, Acute Lung Injury
- What is being tested?
- Liquid oxygen and medical air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Dec 2022to 30 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 1. Healthy non-smoking subjects less than 45 years of age and BMI < 29 kg/m²
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Belfast Health and Social Care Trus
Belfast
Danny McAuley, MD, +442890 972144, d.f.mcauley@qub.ac.uk
Dermot Linden, PhD, 07812008626, dlinden02@qub.ac.uk
About this study
Official title: Effects of Hyperoxia Induced Pulmonary Inflammation and Organ Injury in a Human in Vivo Model
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
- Being tested
- Liquid oxygen, medical air
- Medical subject headings
- Lung Injury, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid oxygenDrug
Also called Liquid medical 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 airDrug
Also called Synthetic 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.
| Study group | Role | What they receive |
|---|---|---|
| Liquid medical oxygen | Active comparator | Liquid medical oxygen will be administered using high-flow nasal cannula delivery system. Receives: Drug: Liquid oxygen |
| Synthetic medical air | Placebo comparator | Synthetic medical air will be administered using high-flow nasal cannula delivery system. Receives: Drug: medical air |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bronchoalveolar lavage Interleukin-8 (IL-8) concentration
To determine the effects of hyperoxia on alveolar inflammatory response
Measured: 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
To determine the effects of hyperoxia on alveolar inflammatory response biomarkers
Measured: 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
To determine the effects of hyperoxia on alveolar protease and antiprotease activity
Measured: 6 hours post-intervention
Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes)
To determine the effects of hyperoxia on alveolar cell populations
Measured: 6 hours post-intervention
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
Measured: 6 and 24 hours post-intervention
Bronchoalveolar lavage soluble programmed cell death receptor (SP-D)
To determine the effects of hyperoxia on alveolar epithelial and endothelial function
Measured: 6 hours post-intervention
Bronchoalveolar lavage total protein
To determine the effects of hyperoxia on alveolar epithelial and endothelial function
Measured: 6 hours post-intervention
Bronchoalveolar lavage receptor for advanced glycation end-products (RAGE)
To determine the effects of hyperoxia on alveolar epithelial and endothelial function
Measured: 6 hours post-intervention
Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE)
To determine the effects of hyperoxia on oxidative stress
Measured: 6 hours post-intervention
Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL)
To determine the effects of hyperoxia on oxidative stress
Measured: 6 hours post-intervention
Plasma advanced glycation end products (AGE)
To determine the effects of hyperoxia on oxidative stress
Measured: 6 and 24 hours post-intervention
Plasma oxidised low density lipoprotein (oxLDL)
To determine the effects of hyperoxia on oxidative stress
Measured: 6 and 24 hours post-intervention
Plasma 4-hydroxy-2-nonenal (4-HNE)
To determine the effects of hyperoxia on oxidative stress
Measured: 6 and 24 hours post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start2 Dec 2022
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oxygen ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Belfast Health and Social Care Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Danny McAuley, MD, Principal investigator, Queen's University, Belfast
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05414370
- Sponsor's protocol ID
- 18129MS-AS
- Status last verified
- Jan 2024
- First submitted
- 11 May 2022
- Last updated
- 29 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Linden D, Dorrian D, Glenn M, Tandel S, Mawhinney T, Welzenbach K, Rowland MJ, Yang M, Klein L, Randazzo E, Sindelar M, Schlotterbeck J, Cattini A, Dushianthan A, Crossley E, McKelvey M, Bailey M, Conlon J, Carr S, Bradley J, Taggart CC, Simpson DA, Kidney J, O'Kane CM, McAuley DF. Effects of hyperoxia on pulmonary inflammation and organ injury in a human in vivo model (HIPI): a randomised controlled trial. Thorax. 2026 Sep 10:thorax-2026-225321. doi: 10.1136/thorax-2026-225321. Online ahead of print.
PubMed 42722424Linden 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.
PubMed 39939102
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Hyperoxia Induced Pulmonary Inflammation and Organ Injury in a Human in Vivo Model
- ClinicalTrials.gov ID
- NCT05414370
- Acronym / sponsor ID
- 18129MS-AS
- Conditions
- Oxygen Toxicity, Pulmonary Injury, Acute Lung Injury
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Belfast Health and Social Care TrustUniversity, hospital or other
- Study start
- 2 Dec 2022 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 10 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liquid medical oxygen | Active comparator | Drug: Liquid oxygenLiquid medical oxygen will be administered using high-flow nasal cannula delivery system. |
| Synthetic medical air | Placebo comparator | Drug: medical airSynthetic medical air will be administered using high-flow nasal cannula delivery system. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 1. Healthy non-smoking subjects less than 45 years of age and BMI < 29 kg/m²
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liquid oxygenAlso: Liquid medical oxygenLiquid 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. | Drug | Liquid medical oxygen |
| medical airAlso: Synthetic medical airSynthetic medical air will be administered for 6 hours using high-flow nasal cannula delivery system with a flow rate of 60 litres per minute. | Drug | Synthetic medical air |
Primary outcome
Bronchoalveolar lavage Interleukin-8 (IL-8) concentration
Time frame: 6 hours post-intervention
To determine the effects of hyperoxia on alveolar inflammatory response
12 secondary outcomes
Bronchoalveolar lavage cytokines including but not limited to tumour necrosis factor alpha, IL-1 beta and IL-6
Time frame: 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
Time frame: 6 hours post-intervention
Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes)
Time frame: 6 hours post-intervention
Plasma cytokines including but not limited to IL-8, tumour necrosis factor alpha, IL-1 beta and IL-6
Time frame: 6 and 24 hours post-intervention
Bronchoalveolar lavage soluble programmed cell death receptor (SP-D)
Time frame: 6 hours post-intervention
Bronchoalveolar lavage total protein
Time frame: 6 hours post-intervention
Bronchoalveolar lavage receptor for advanced glycation end-products (RAGE)
Time frame: 6 hours post-intervention
Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE)
Time frame: 6 hours post-intervention
Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL)
Time frame: 6 hours post-intervention
Plasma advanced glycation end products (AGE)
Time frame: 6 and 24 hours post-intervention
Plasma oxidised low density lipoprotein (oxLDL)
Time frame: 6 and 24 hours post-intervention
Plasma 4-hydroxy-2-nonenal (4-HNE)
Time frame: 6 and 24 hours post-intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2024.
- Derived from this study: PubMed 42722424Linden D, Dorrian D, Glenn M, Tandel S, Mawhinney T, Welzenbach K, Rowland MJ, Yang M, Klein L, Randazzo E, Sindelar M, Schlotterbeck J, Cattini A, Dushianthan A, Crossley E, McKelvey M, Bailey M, Conlon J, Carr S, Bradley J, Taggart CC, Simpson DA, Kidney J, O'Kane CM, McAuley DF. Effects of hyperoxia on pulmonary inflammation and organ injury in a human in vivo model (HIPI): a randomised controlled trial. Thorax. 2026 Sep 10:thorax-2026-225321. doi: 10.1136/thorax-2026-225321. Online ahead of print.
- Derived from this study: PubMed 39939102Linden 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Danny McAuley, MD principal investigator
Queen's University, Belfast
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liquid oxygen and medical air in people with Oxygen Toxicity and Pulmonary Injury, run by Belfast Health and Social Care Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Danny McAuley, MD (+442890 972144, d.f.mcauley@qub.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bronchoalveolar lavage Interleukin-8 (IL-8) concentration (time frame: 6 hours post-intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05414370, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2024.