Effect of Hydrogen Gas on Hyperbaric Oxygen Toxicity

NCT07263399 | Not Yet Recruiting

• 2 other identifiers: BTH-6.1.1-0165-20255005113/22FMV2951
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Hyperbaric Oxygen; Healthy Subjects (HS); Diving Medicine; Hydrogen-oxygen Gas; Oxygen Toxicity; Oxidative Stress; Hyperoxia

Keywords

Pulmonary Oxygen Toxicity; Hydrogen Gas; Diving Physiology; Lung Function; Hyperbaric Oxygen; Human Study; Military Divers

Outcome Measures

Primary Outcomes (1)

• 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.

  Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.

Secondary Outcomes (15)

• Forced Expiratory Volume in One Second (FEV₁)

  Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure

• Change in FEV₁/FVC ratio

  Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure

• Change in Forced Expiratory Flow 25-75% (FEF25-75%)

  Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.

• Change in Peak Expiratory Flow (PEF)

  Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.

• Change in Inspiratory Capacity (IC)

  Pre-exposure, 30-120 minutes post-exposure, and 24-36 hours post-exposure.

Other Outcomes (1)

• Anthropometric Measurements (Weight, Height, Sex, Age, BMI)

  Baseline (Pre-exposure, prior to first dive session)

Study Arms (2)

Hydrogen Gas Intervention

EXPERIMENTAL

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

Nitrogen Gas Control

ACTIVE COMPARATOR

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

Interventions

Inhaled Hydrogen-Enriched Oxygen Gas OTHER

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.

Hydrogen Gas Intervention; Nitrogen Gas Control

Inhaled Nitrogen-Enriched Oxygen Gas OTHER

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.

Hydrogen Gas Intervention; Nitrogen Gas Control

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Blekinge Institute of Technology: lead
• Karolinska Institutet: collaborator
• Göteborg University: collaborator
• Lund University: collaborator
• Swedish Armed Forces Diving and Naval Medicine Centre: collaborator

Study Sites (2)

Blekinge Institute of Technology

Karlskrona, Blekinge County, 37179, Sweden

Location

Swedish Armed Forces Diving and Naval Medicine Centre (DNC)

Karlskrona, Sweden

Location

Related Publications (4)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

MeSH Terms

Conditions

Hyperoxia

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

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

Model Details: This is a human randomized, double-blind, crossover trial in which each participant undergoes two separate hyperbaric oxygen exposures: one with hydrogen-enriched breathing gas (1-2% H₂) and one with nitrogen-enriched breathing gas (1-2% N₂) as control. Before and after each exposure session, participants complete standardized pulmonary function tests and provide blood and urin samples for analysis of oxidative stress biomarkers. A washout period of at least two weeks is maintained between sessions to minimize carryover effects.

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: December 4, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

SE (2)