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Oxygen Toxicity: Mechanisms in Humans

Primary Purpose

Oxygen Toxicity, Hypercapnia, Seizures

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Sleep Deprivation
Caffeine
Methylphenidate
Carbon Dioxide
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Oxygen Toxicity

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Active Comparator

    Experimental

    Experimental

    Experimental

    Arm Label

    Sleep Deprivation

    Caffeine

    Methylphenidate

    Carbon Dioxide Exposure

    Arm 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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Hypercapnic ventiltaory response

    Secondary Outcome Measures

    Lactate, pyruvate
    Arterial PCO2
    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).
    Cerebral blood oxygenation
    Hormone levels (leptin, adiponectin)

    Full Information

    First Posted
    February 6, 2023
    Last Updated
    February 27, 2023
    Sponsor
    Duke University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05761756
    Brief Title
    Oxygen Toxicity: Mechanisms in Humans
    Official Title
    Applied Physiology of Oxygen Toxicity: Mechanisms in Humans
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2023 (Anticipated)
    Primary Completion Date
    March 2026 (Anticipated)
    Study Completion Date
    March 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Duke University

    4. Oversight

    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
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Oxygen Toxicity, Hypercapnia, Seizures

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Investigator
    Allocation
    Randomized
    Enrollment
    62 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Sleep Deprivation
    Arm Type
    Active Comparator
    Arm 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.
    Arm Title
    Caffeine
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Methylphenidate
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Carbon Dioxide Exposure
    Arm Type
    Experimental
    Arm 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.
    Intervention Type
    Behavioral
    Intervention Name(s)
    Sleep Deprivation
    Intervention Description
    24 hours sleep deprivation
    Intervention Type
    Drug
    Intervention Name(s)
    Caffeine
    Intervention Description
    Oral administration of caffeine
    Intervention Type
    Drug
    Intervention Name(s)
    Methylphenidate
    Intervention Description
    Oral administration of methylphenidate
    Intervention Type
    Drug
    Intervention Name(s)
    Carbon Dioxide
    Intervention Description
    Oral administration of sodium bicarbonate to simulate carbon dioxide exposure
    Primary Outcome Measure Information:
    Title
    Hypercapnic ventiltaory response
    Time Frame
    Baseline and after Intervention/arm, which averages 3 months
    Secondary Outcome Measure Information:
    Title
    Lactate, pyruvate
    Time Frame
    Baseline and after intervention/arm, which averages 3 months
    Title
    Arterial PCO2
    Time Frame
    Baseline and after Intervention/arm
    Title
    Integrated diaphragmatic function (IDF) composite score
    Description
    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).
    Time Frame
    Baseline and after Intervention/arm, which averages 3 months
    Title
    Cerebral blood oxygenation
    Time Frame
    Baseline and after Intervention/arm, which averages 3 months
    Title
    Hormone levels (leptin, adiponectin)
    Time Frame
    Baseline and after Intervention/arm, which averages 3 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Derek B Covington, MD
    Phone
    919-613-8881
    Email
    derek.covington@duke.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Richard Moon, MD
    Phone
    919-613-8881
    Email
    Richard.moon@duke.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Derek B Covington, MD
    Organizational Affiliation
    Duke University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
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    Citation
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    Oxygen Toxicity: Mechanisms in Humans

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