Oxygen Toxicity: Mechanisms in Humans

October 21, 2025 updated by: Duke University

Applied Physiology of Oxygen Toxicity: Mechanisms in Humans

The goal of this clinical trial is to learn about the mechanisms of oxygen toxicity in scuba divers. The main questions it aims to answer are:

  • How does the training of respiratory muscles affect oxygen toxicity?
  • How do environmental factors, such as sleep deprivation, the ingestion of commonly utilized medications, and chronic exposure to carbon dioxide, impact the risk of oxygen toxicity?
  • How does immersion in water affect the development of oxygen toxicity?

Participants will be asked to do the following:

  • Undergo a basic screening exam composed of health history, vital signs, and some respiratory function tests
  • Train their respiratory muscles at regular intervals
  • Exercise on a cycle ergometer both in dry conditions and underwater/under pressure in the context of medication, sleep deprivation, or carbon dioxide exposure

Researchers will compare the performance of each subject before and after the possible interventions described above to see if there are changes in exercise performance, respiratory function, cerebral blood flow, and levels of gene expression.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke University Health Sustem
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Equal numbers of male and female
  • Non-smokers
  • Aged 18-45 years
  • Males will be required to have VO2 peak > or equal to mL/kg min
  • and females > or equal to 30 mL/kg min

Exclusion Criteria:

  • Pregnancy
  • Cardiorespiratory disease, including hypertension
  • Neuromuscular disease
  • Anemia
  • History of hemoglobinopathy, including sick cell disease and trait

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sleep Deprivation
Effect of sleep deprivation on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Ten subjects will be tested before and after 24 hours of sleep deprivation. The order of sleep deprivation vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water.
Behavioral: Sleep Deprivation
24 hours sleep deprivation
Experimental: Caffeine
Effect of caffeine and methylphenidate on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Twenty subjects will be similarly sleep-deprived, tested as above and then re-tested tested following oral administration of administration of either oral caffeine (N=10) or methylphenidate (N=10). Pre-dive caffeine will be administered 500 mg orally [59]. Pre-dive methylphenidate will be administered as a single dose of 5 mg [60]. The order of drug administration vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water. fNIRS will be used to assess cerebral oxygenation and regional blood volume.
Drug: Caffeine
Oral administration of caffeine
Experimental: Methylphenidate
Effect of caffeine and methylphenidate on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Twenty subjects will be similarly sleep-deprived, tested as above and then re-tested tested following oral administration of administration of either oral caffeine (N=10) or methylphenidate (N=10). Pre-dive caffeine will be administered 500 mg orally [59]. Pre-dive methylphenidate will be administered as a single dose of 5 mg [60]. The order of drug administration vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water. fNIRS will be used to assess cerebral oxygenation and regional blood volume.
Drug: Methylphenidate
Oral administration of methylphenidate
Experimental: Carbon Dioxide Exposure
Effect of simulated chronic CO2 exposure on HCVR and arterial PCO2 during submersed rest and exercise at 98 fsw. Ten subjects will be studied before and after induction of metabolic alkalosis as described above with daily oral administration of sodium bicarbonate. Oral bicarbonate to simulate hypercapnia exposure will seek to increase serum bicarbonate to 30 mM/L via daily oral intake of 6 teaspoons of NaHCO3 for five days. Subsequently, blood will be drawn and intake adjusted as necessary [61]. The order of alkalization vs. control will be randomized. Measurements at 98 fsw will be obtained at rest and during 10 minutes of moderate exercise in thermoneutral (29-30°C) water.
Drug: Carbon Dioxide
Oral administration of sodium bicarbonate to simulate carbon dioxide exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Hypercapnic ventilatory response
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Arterial PCO2
Time Frame: Baseline and after Intervention/arm
Baseline and after Intervention/arm
Integrated diaphragmatic function (IDF) composite score
Time Frame: Baseline and after Intervention/arm, which averages 3 months
A composite score comprised of maximum breathing capacity (MBC), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and diaphragmatic thickness will be used as the measure of Integrated diaphragmatic function (IDF).
Baseline and after Intervention/arm, which averages 3 months
Cerebral blood oxygenation
Time Frame: Baseline and after Intervention/arm, which averages 3 months
Baseline and after Intervention/arm, which averages 3 months
Hormone levels (leptin, adiponectin)
Time Frame: Baseline and after Intervention/arm, which averages 3 months
Baseline and after Intervention/arm, which averages 3 months
Lactate, pyruvate
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Investigators

  • Principal Investigator: Derek B Covington, MD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 28, 2023

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

August 31, 2026

Study Registration Dates

First Submitted

February 6, 2023

First Submitted That Met QC Criteria

February 27, 2023

First Posted (Actual)

March 9, 2023

Study Record Updates

Last Update Posted (Estimated)

October 23, 2025

Last Update Submitted That Met QC Criteria

October 21, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00112396

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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