Oxygen Toxicity: Mechanisms in Humans

Seizures Clinical Trial

Official title:

Applied Physiology of Oxygen Toxicity: Mechanisms in Humans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05761756
• Other study ID #: Pro00112396
• Status: Recruiting
• Phase: N/A
• Start date: November 28, 2023
• Est. completion date: March 2026

Study information

• Verified date: January 2024
• Source: Duke University
• Contact: Derek B Covington, MD
• Phone: 919-613-8881
• Email: derek.covington[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercapnia
• Hyperoxia
• Oxygen Toxicity
• Seizures

Intervention

Behavioral:
• Sleep Deprivation
24 hours sleep deprivation

Drug:
• Caffeine
Oral administration of caffeine
• Methylphenidate
Oral administration of methylphenidate
• Carbon Dioxide
Oral administration of sodium bicarbonate to simulate carbon dioxide exposure

Locations

Country	Name	City	State
United States	Duke University Health Sustem	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hypercapnic ventilatory response		3 months
Secondary	Lactate, pyruvate		3 months
Secondary	Arterial PCO2		Baseline and after Intervention/arm
Secondary	Integrated diaphragmatic function (IDF) composite score	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
Secondary	Cerebral blood oxygenation		Baseline and after Intervention/arm, which averages 3 months
Secondary	Hormone levels (leptin, adiponectin)		Baseline and after Intervention/arm, which averages 3 months