Oxygen Toxicity: Mechanisms in Humans

Duke University

Status: Enrolling

Conditions: Seizures; Hypercapnia; Oxygen Toxicity

Treatments: Drug: Methylphenidate; Drug: Caffeine; Drug: Carbon Dioxide; Behavioral: Sleep Deprivation

Study type: Interventional

Funder types: Other

Identifiers

NCT05761756

Pro00112396

Details and patient eligibility

About

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.

Enrollment: 62 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

62 participants in 4 patient groups

Sleep Deprivation

Active Comparator group

Description:

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.

Treatment:

Behavioral: Sleep Deprivation

Caffeine

Experimental group

Description:

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.

Treatment:

Drug: Caffeine

Methylphenidate

Experimental group

Description:

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.

Treatment:

Drug: Methylphenidate

Carbon Dioxide Exposure

Experimental group

Description:

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.

Treatment:

Drug: Carbon Dioxide