An interventional study of Inhaled Hydrogen-Enriched Oxygen Gas and Inhaled Nitrogen-Enriched Oxygen Gas in Oxygen Toxicity, Oxidative Stress and Hyperoxia, sponsored by Blekinge Institute of Technology. Not yet recruiting at 2 sites in Sweden. Open to participants aged 20 Years to 64 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-04.
Sponsored by Blekinge Institute of Technology · Not applicable, Interventional, and Basic science
The goal of this trial is to investigate whether adding a small fraction of hydrogen gas to an oxygen-enriched breathing mixture can reduce pulmonary oxygen toxicity (POT) in healthy and active divers from the Swedish Armed Forces. The main questions it aims to answer are:
Researchers will compare oxygen-enriched breathing gas with 1-2% hydrogen to oxygen-enriched gas with 1-2% nitrogen (control) to see if hydrogen provides protective effects against POT during hyperbaric exposure.
Participants will:
Exclusion Criteria:
In this arm, participants will undergo a single hyperbaric exposure breathing a gas mixture composed of 98-99% oxygen and 1-2% hydrogen (H₂) at a partial pressure of 1.75 ATA for 240 minutes. The intervention aims to evaluate whether hydrogen gas has protective effects against pulmonary oxygen toxicity. Pulmonary function tests and blood and urin sampling for oxidative stress biomarkers will be performed both before and after the exposure session. The order of intervention and control exposures is randomized and the study is conducted in a double-blind fashion. A washout period of at least two weeks will follow before the control
Other: Inhaled Hydrogen-Enriched Oxygen Gas · Other: Inhaled Nitrogen-Enriched Oxygen Gas
In this arm, participants will undergo a single hyperbaric exposure breathing a gas mixture composed of 98-99% oxygen and 1-2% nitrogen (N₂) at a partial pressure of 1.75 ATA for 240 minutes. This exposure serves as the control condition and represents the standard oxygen-enriched breathing gas currently in use. Pulmonary function tests and blood and urin sampling for oxidative stress biomarkers will be performed both before and after the exposure session. Participants will be randomized to the order of exposures, and both participants and investigators will be blinded to the gas composition. A washout period of at least two weeks will follow before the intervention.
Other: Inhaled Hydrogen-Enriched Oxygen Gas · Other: Inhaled Nitrogen-Enriched Oxygen Gas
Participants will inhale a gas mixture consisting of 98-99% oxygen and 1-2% hydrogen via a breathing circuit during a single hyperbaric exposure. The exposure will be conducted at a partial pressure of 1.75 ATA for 240 minutes. The intervention aims to evaluate the protective effect of hydrogen gas against pulmonary oxygen toxicity.
Participants will inhale a gas mixture consisting of 98-99% oxygen and 1-2% nitrogen via a breathing circuit during a single hyperbaric exposure. The exposure will be conducted at a partial pressure of 1.75 ATA for 240 minutes. The intervention aims to evaluate the protective effect of hydrogen gas against pulmonary oxygen toxicity.
Change in Vital Capacity (ΔVC)
Absolute change in vital capacity (VC), calculated as the difference in liters (L) between pre-exposure and post-exposure spirometry values, measured after each hyperbaric oxygen exposure session.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Forced Expiratory Volume in One Second (FEV₁)
As part of the spirometric and plethysmographic measurements, Forced Expiratory Volume in 1 second (FEV₁) will be analyzed. This represents the change (ΔFEV₁) in liters (L) between pre- and post-exposure spirometry, indicating expiratory flow capacity. Measurements follow ATS/ERS 2019 standards.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure
Change in FEV₁/FVC ratio
As part of the spirometric and plethysmographic measurements, the ratio between Forced Expiratory Volume in 1 second and Forced Vital Capacity (FEV₁/FVC) will be calculated. The change (ΔFEV₁/FVC) is expressed as a percentage (%) to assess airflow limitation or restriction following hyperbaric oxygen exposure.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure
Change in Forced Expiratory Flow 25-75% (FEF25-75%)
As part of the spirometric and plethysmographic measurements, the mid-expiratory flow (FEF25-75%) will be assessed. This parameter reflects the mean expiratory flow between 25% and 75% of FVC and serves as an indicator of small airway function. Values are expressed in liters per second (L/s).
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Change in Peak Expiratory Flow (PEF)
As part of the spirometric and plethysmographic measurements, Peak Expiratory Flow (PEF) will be analyzed. The change (ΔPEF) represents the maximum flow achieved during forced exhalation, measured in liters per second (L/s). This outcome evaluates large airway performance.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Change in Inspiratory Capacity (IC)
As part of the spirometric and plethysmographic measurements, Inspiratory Capacity (IC) will be determined. The change (ΔIC) in liters (L) reflects the maximal volume of air that can be inspired after a normal exhalation, providing insight into potential restrictive changes following exposure.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Change in Total Lung Capacity (TLC)
As part of the spirometric and plethysmographic measurements, Total Lung Capacity (TLC) will be assessed. The change (Δ TLC) in liters (L) represents the total volume of air contained in the lungs after maximal inspiration, used to detect restrictive or hyperinflation patterns following hyperbaric oxygen exposure.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Residual Volume (Δ RV)
As part of the spirometric and plethysmographic measurements, Residual Volume (RV) will be assessed. The change (Δ RV) in liters (L) represents the volume of air remaining in the lungs after maximal exhalation, used to detect gas-trapping or hyperinflation patterns associated with pulmonary oxygen toxicity
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Functional Residual Capacity (Δ FRC)
As part of the spirometric and plethysmographic measurements, Functional Residual Capacity (FRC) will be assessed. The change (Δ FRC) in liters (L) represents the volume of air remaining in the lungs at the end of a normal tidal exhalation, used to detect early alterations in lung compliance or airway closure during hyperbaric oxygen exposure.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Change in Diffusing Capacity for Carbon Monoxide (ΔDLCO)
Absolute change in lung diffusing capacity for carbon monoxide (DLCO) , measured (mmol/min/lkPa) with single-breath DLCO test before and after each exposure, to evaluate alveolar-capillary gas exchange efficiency. DLCO values are adjusted for hemoglobin levels to improve measurement accuracy.
Time frame: Pre-exposure, 30-120 minutes post-exposure and 24-36 hours post-exposure.
Airway Resistance (Impulse Oscillometry, Tremoflo™)
Assessment of central and peripheral airway resistance (R5, R20, X5) using impulse oscillometry (Tremoflo™) before and after exposure. Evaluates small airway mechanics related to hyperbaric oxygen exposure with or without hydrogen supplementation. Unit of Measurement: cmH₂O·s/L
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Index of Oxygen Stress (ΔiOS)
Composite index derived from impulse oscillometry (Tremoflo™) representing the mean relative change from baseline in airway impedance parameters (R5, R20, X5). The Index of Oxygen Stress (iOS) quantifies oxidative stress-related changes in small airway mechanics following hyperbaric oxygen exposure with or without hydrogen supplementation.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Change in Fractional Exhaled Nitric Oxide (ΔFeNO)
Measurement of airway inflammation and oxidative stress via fractional exhaled nitric oxide (FeNO) levels measured in parts per billion (ppb).
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Change in Exhaled Breath Particle Analysis (ΔPExA)
Change in exhaled particle count and biochemical composition (lipids, proteins, coagulation factors) reflecting epithelial lining fluid alterations.
Time frame: Pre-exposure and follow-up 24-36 hours post-exposure after each intervention.
Blood and Urinary Biomarkers of Oxidative Stress and Inflammation
Analysis of venous blood and urine samples for biomarkers of oxidative stress (e.g., 8-isoprostane, MDA, 8-OHdG) and inflammation (e.g., IL-6, TNF-α) to evaluate systemic effects of hyperbaric oxygen exposure with or without hydrogen supplementation. Concentrations will be quantified in standard laboratory units, for example ng/mL, pg/mL, or other equivalent measures.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Biomarkers of Neuronal Injury
Analysis of venous plasma samples for fluid biomarkers of neuronal injury (e.g., NfL, GFAP, Tau, UCH-L1) using NULISA™ or Simoa® HD-1 assay technologies, to evaluate central nervous system effects of hyperbaric oxygen exposure with or without hydrogen supplementation. Concentrations will be quantified in pg/mL.
Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.
Anthropometric Measurements (Weight, Height, Sex, Age, BMI)
Anthropometric data will be recorded to assess body composition and physical characteristics of the study population and to enable adjustment for potential confounders in pulmonary function outcomes. This includes body weight (kg), height (cm), biological sex (M/F), age (years), and body mass index (BMI). These variables will not serve as primary endpoints but will describe baseline characteristics and support interpretation of within-subject changes in lung function.
Time frame: Baseline (Pre-exposure, prior to first dive session)
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Blekinge Institute of Technology