Oxygen Toxicity: Mechanisms in Humans

Not Applicable

Recruiting

• Conditions: Seizures; Oxygen Toxicity; Hypercapnia
• Interventions: Behavioral: Sleep Deprivation; Drug: Caffeine; Drug: Methylphenidate; Drug: Carbon Dioxide

• Registration Number: NCT05761756
• Lead Sponsor: Duke University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-06
• Study First Submitted QC: 2023-02-27
• Study First Posted: 2023-03-09
• Study Start: 2023-11-28
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-17
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 62

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sleep Deprivation	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.
Caffeine	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.
Methylphenidate	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.
Carbon Dioxide Exposure	Carbon Dioxide	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.

Primary Outcome Measures

Name	Time	Method
Hypercapnic ventilatory response	3 months

Secondary Outcome Measures

Name	Time	Method
Cerebral blood oxygenation	Baseline and after Intervention/arm, which averages 3 months
Hormone levels (leptin, adiponectin)	Baseline and after Intervention/arm, which averages 3 months
Lactate, pyruvate	3 months
Integrated diaphragmatic function (IDF) composite score	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).
Arterial PCO2	Baseline and after Intervention/arm

Trial Locations

Locations (1)

Duke University Health Sustem; 🇺🇸 Durham, North Carolina, United States