Oxygen Toxicity: Mechanisms in Humans

NCT ID: NCT05761756

Last Updated: 2025-10-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-28

Study Completion Date

2026-08-31

Brief Summary

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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

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Conditions

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Oxygen Toxicity Hypercapnia Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Investigators

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Sleep Deprivation

Intervention Type BEHAVIORAL

24 hours sleep deprivation

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.

Group Type EXPERIMENTAL

Caffeine

Intervention Type DRUG

Oral administration of caffeine

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.

Group Type EXPERIMENTAL

Methylphenidate

Intervention Type DRUG

Oral administration of methylphenidate

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.

Group Type EXPERIMENTAL

Carbon Dioxide

Intervention Type DRUG

Oral administration of sodium bicarbonate to simulate carbon dioxide exposure

Interventions

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Sleep Deprivation

24 hours sleep deprivation

Intervention Type BEHAVIORAL

Caffeine

Oral administration of caffeine

Intervention Type DRUG

Methylphenidate

Oral administration of methylphenidate

Intervention Type DRUG

Carbon Dioxide

Oral administration of sodium bicarbonate to simulate carbon dioxide exposure

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Derek B Covington, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Duke University Health Sustem

Durham, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Derek B Covington, MD

Role: CONTACT

919-613-8881

Richard Moon, MD

Role: CONTACT

919-613-8881

Facility Contacts

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Derek Covington, M.D.

Role: primary

919-613-8881

References

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Dunworth SA, Natoli MJ, Cooter M, Cherry AD, Peacher DF, Potter JF, Wester TE, Freiberger JJ, Moon RE. Hypercapnia in diving: a review of CO(2) retention in submersed exercise at depth. Undersea Hyperb Med. 2017 May-Jun;44(3):191-209. doi: 10.22462/5.6.2017.1.

Reference Type BACKGROUND
PMID: 28779577 (View on PubMed)

Drummond JC. Blood Pressure and the Brain: How Low Can You Go? Anesth Analg. 2019 Apr;128(4):759-771. doi: 10.1213/ANE.0000000000004034.

Reference Type BACKGROUND
PMID: 30883421 (View on PubMed)

Lucas SJ, Tzeng YC, Galvin SD, Thomas KN, Ogoh S, Ainslie PN. Influence of changes in blood pressure on cerebral perfusion and oxygenation. Hypertension. 2010 Mar;55(3):698-705. doi: 10.1161/HYPERTENSIONAHA.109.146290. Epub 2010 Jan 18.

Reference Type BACKGROUND
PMID: 20083726 (View on PubMed)

Wester TE, Cherry AD, Pollock NW, Freiberger JJ, Natoli MJ, Schinazi EA, Doar PO, Boso AE, Alford EL, Walker AJ, Uguccioni DM, Kernagis D, Moon RE. Effects of head and body cooling on hemodynamics during immersed prone exercise at 1 ATA. J Appl Physiol (1985). 2009 Feb;106(2):691-700. doi: 10.1152/japplphysiol.91237.2008. Epub 2008 Nov 20.

Reference Type BACKGROUND
PMID: 19023017 (View on PubMed)

Pendergast DR, Moon RE, Krasney JJ, Held HE, Zamparo P. Human Physiology in an Aquatic Environment. Compr Physiol. 2015 Sep 20;5(4):1705-50. doi: 10.1002/cphy.c140018.

Reference Type BACKGROUND
PMID: 26426465 (View on PubMed)

Linnarsson D, Ostlund A, Lind F, Hesser CM. Hyperbaric bradycardia and hypoventilation in exercising men: effects of ambient pressure and breathing gas. J Appl Physiol (1985). 1999 Oct;87(4):1428-32. doi: 10.1152/jappl.1999.87.4.1428.

Reference Type BACKGROUND
PMID: 10517774 (View on PubMed)

Oppersma E, Doorduin J, van der Hoeven JG, Veltink PH, van Hees HWH, Heunks LMA. The effect of metabolic alkalosis on the ventilatory response in healthy subjects. Respir Physiol Neurobiol. 2018 Feb;249:47-53. doi: 10.1016/j.resp.2018.01.002. Epub 2018 Jan 4.

Reference Type BACKGROUND
PMID: 29307724 (View on PubMed)

Cherry AD, Forkner IF, Frederick HJ, Natoli MJ, Schinazi EA, Longphre JP, Conard JL, White WD, Freiberger JJ, Stolp BW, Pollock NW, Doar PO, Boso AE, Alford EL, Walker AJ, Ma AC, Rhodes MA, Moon RE. Predictors of increased PaCO2 during immersed prone exercise at 4.7 ATA. J Appl Physiol (1985). 2009 Jan;106(1):316-25. doi: 10.1152/japplphysiol.00885.2007. Epub 2008 Sep 11.

Reference Type BACKGROUND
PMID: 18787095 (View on PubMed)

Dodson ME, Fryer JM. Postoperative effects of methylphenidate. Br J Anaesth. 1980 Dec;52(12):1265-70. doi: 10.1093/bja/52.12.1265.

Reference Type BACKGROUND
PMID: 7004471 (View on PubMed)

GALE AS. The effect of methylphenidate (ritalin) on thiopental recovery. Anesthesiology. 1958 Jul-Aug;19(4):521-31. doi: 10.1097/00000542-195807000-00009. No abstract available.

Reference Type BACKGROUND
PMID: 13545587 (View on PubMed)

Beecroft J, Duffin J, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease. Eur Respir J. 2006 Jul;28(1):151-8. doi: 10.1183/09031936.06.00075405. Epub 2006 Mar 1.

Reference Type BACKGROUND
PMID: 16510459 (View on PubMed)

Yao Q, Pho H, Kirkness J, Ladenheim EE, Bi S, Moran TH, Fuller DD, Schwartz AR, Polotsky VY. Localizing Effects of Leptin on Upper Airway and Respiratory Control during Sleep. Sleep. 2016 May 1;39(5):1097-106. doi: 10.5665/sleep.5762.

Reference Type BACKGROUND
PMID: 26951402 (View on PubMed)

Eynan M, Arieli Y, Taran B, Yanir Y. Symptoms of central nervous system oxygen toxicity during 100% oxygen breathing at normobaric pressure with increasing inspired levels of carbon dioxide: a case report. Diving Hyperb Med. 2020 Mar 31;50(1):70-74. doi: 10.28920/dhm50.1.70-74.

Reference Type BACKGROUND
PMID: 32187621 (View on PubMed)

Martin BJ. Effect of sleep deprivation on tolerance of prolonged exercise. Eur J Appl Physiol Occup Physiol. 1981;47(4):345-54. doi: 10.1007/BF02332962.

Reference Type BACKGROUND
PMID: 7199438 (View on PubMed)

Other Identifiers

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Pro00112396

Identifier Type: -

Identifier Source: org_study_id

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