Effect of Hydrogen Gas on Hyperbaric Oxygen Toxicity

Official title

Effect of Hydrogen Gas on Hyperbaric Oxygen Toxicity - A Randomized Controlled Cross-Over Trial

Overview

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: * Does hydrogen gas reduce oxidative stress and changes in pulmonary function associated with prolonged hyperbaric oxygen exposure? * What are the underlying pathophysiological mechanisms of pulmonary oxygen toxicity? 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: * Complete two hyperbaric exposure sessions (hydrogen vs. nitrogen), each lasting 240 minutes at 1.75 ATA * Undergo pulmonary function tests and sampling of blod and urin before and after each session * Serve as their own controls in a double-blind, randomized, crossover study design

Interventions

• Other Inhaled Hydrogen-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.
• Other Inhaled Nitrogen-Enriched Oxygen Gas
  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.

Primary outcome measures

• Change in Vital Capacity (ΔVC) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]

Secondary outcome measures (12)

• Forced Expiratory Volume in One Second (FEV₁) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure]
• Change in FEV₁/FVC ratio [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure]
• Change in Forced Expiratory Flow 25-75% (FEF25-75%) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Change in Peak Expiratory Flow (PEF) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Change in Inspiratory Capacity (IC) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Change in Total Lung Capacity (TLC) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Residual Volume (Δ RV) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Functional Residual Capacity (Δ FRC) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Change in Diffusing Capacity for Carbon Monoxide (ΔDLCO) [Time frame: Pre-exposure, 30-120 minutes post-exposure and 24-36 hours post-exposure.]
• Airway Resistance (Impulse Oscillometry, Tremoflo™) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Index of Oxygen Stress (ΔiOS) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]
• Change in Fractional Exhaled Nitric Oxide (ΔFeNO) [Time frame: Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.]

Eligibility criteria

Inclusion criteria

• Military divers actively serving, aged 20-64 years
• Meeting the Swedish Armed Forces physical standards for diving

Exclusion criteria

• Ongoing infection or illness that may impact pulmonary function
• Use of alcohol or smoking cigarettes within 48 hours
• Diving with any breathing gas within 48 hours
• Diving with oxygen-enriched gas (100% O₂) within 2 weeks
• Use of medications that could affect oxidative stress, lung function, or neurological status
• Medical history of serious diving-related injuries or long-term complications

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Basic science

Study locations

Sweden · 2 centers

• Blekinge Institute of Technology — Karlskrona
• Swedish Armed Forces Diving and Naval Medicine Centre (DNC) — Karlskrona

Publications

• de Jong FJM, Wingelaar TT, van Hulst RA. Pulmonary oxygen toxicity in occupational diving. Occup Med (Lond). 2023 Jun 26;73(5):231-232. doi: 10.1093/occmed/kqad043. PMID 37364027
• Kawamura T, Wakabayashi N, Shigemura N, Huang CS, Masutani K, Tanaka Y, Noda K, Peng X, Takahashi T, Billiar TR, Okumura M, Toyoda Y, Kensler TW, Nakao A. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. Am J Physiol Lung Cell Mol Physiol. 2013 May 15;304(10):L646-56. doi: 10.1152/ajplung.00164.2012. Epub 2013 Mar 8. PMID 23475767
• Yildiz F, LeBaron TW, Alwazeer D. A comprehensive review of molecular hydrogen as a novel nutrition therapy in relieving oxidative stress and diseases: Mechanisms and perspectives. Biochem Biophys Rep. 2025 Jan 25;41:101933. doi: 10.1016/j.bbrep.2025.101933. eCollection 2025 Mar. PMID 39911528
• Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007 Jun;13(6):688-94. doi: 10.1038/nm1577. Epub 2007 May 7. PMID 17486089

Identifiers

NCT: NCT07263399 · BTH-6.1.1-0165-2025 · 5005113/22FMV2951

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗