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Effects of Pre-dive Ketone Food Products on Latency to CNS Oxygen Toxicity (Aim 2)

Primary Purpose

Oxygen Toxicity

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Ketogenic food products
Control: Placebo
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 - 39 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Males & females between 18 and 39 years old. Measured (Phase 2) VO2max ≥ 30 ml/kg/min (female) or 35 ml/kg/min (male). BMI ≤ 30.0 unless VO2max and baseline exercise profile is deemed appropriate for the study by the PI. (Phase 2 only) Able to exercise continuously on cycle ergometer for 2 hours. (Phase 2 only) Able to equalize middle ears and tolerate hyperbaric chamber exposure test. Exclusion Criteria: Prolonged QTc on initial ECG Currently pregnant or attempting to become pregnant. Have a medical history of: Smoking history deemed significant by PI Known significant electrolyte disorders Coronary artery disease Cardiac arrhythmia deemed significant by PI Lung disease Hypertension Seizures Exercise intolerance or inability to meet inclusion requirements Psychiatric disorder deemed significant by PI Previous pneumothorax or pneumomediastinum Hypo- or hyperglycemia Diabetes Inability to equalize middle ear spaces during hyperbaric compression Claustrophobia Regularly take any medications which may alter heart rate, blood pressure, neurotransmitter function, alter seizure threshold, mood or affect per PI discretion. Any other condition limiting ability to perform exercise testing or dive profile as determined by the investigators.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Experimental: Ketogenic food products

    Control: Placebo

    Arm Description

    Dietary Supplement: Ketogenic food products Participants will be given a ketogenic food product prior to the hyperbaric oxygen exposure.

    Dietary Supplement comparator

    Outcomes

    Primary Outcome Measures

    Latency to central nervous system oxygen toxicity (CNSOT)
    Assessment of latency to CNSOT in a simulated working dive breathing 100% oxygen at 2.06 ATA, immersed in water (head out), in a hyperbaric chamber while performing exercise. Endpoint is time to development of signs or symptoms of CNSOT. Maximum duration 120 minutes.

    Secondary Outcome Measures

    Cognitive performance
    Changes in Multi Attribute Test battery scores prior to and during hyperbaric exposure. Tracking score pixel distance from target center, scale min = 0, no defined maximum.
    Level of nutritional ketosis as detected by serume beta hydroxybutyrate levels
    Measure serume beta hydroxybutyrate levels in blood samples
    Number of participants with change in EEG
    Changes in visual EEG inspection prior to and during hyperbaric exposure.
    Change in qEEG alpha/delta power ratio (ratio of power in alpha frequency band to power in delta frequency band)
    Changes in qEEG readings prior to and during hyperbaric exposure
    Change in end-tidal CO2
    Changes in end-tidal CO2 levels in blood samples prior to and during hyperbaric exposure
    Change in venous CO2
    Changes in CO2 levels in blood samples prior to and during hyperbaric exposure
    Change in heart rate
    Changes in heart rate prior to and during hyperbaric exposure
    Change in ventilatory rate
    Changes in ventilatory rate prior to and during hyperbaric exposure
    Number of participants who develop CNS oxygen toxicity
    Any symptoms of CNSOT during hyperbaric exposure as described by participants will be recorded.

    Full Information

    First Posted
    March 24, 2023
    Last Updated
    July 12, 2023
    Sponsor
    Duke University
    Collaborators
    United States Navy
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05831228
    Brief Title
    Effects of Pre-dive Ketone Food Products on Latency to CNS Oxygen Toxicity (Aim 2)
    Official Title
    Effects of Pre-dive Ketone Food Products on Latency to Central Nervous System Oxygen Toxicity
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    March 30, 2024 (Anticipated)
    Study Completion Date
    March 30, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Duke University
    Collaborators
    United States Navy

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to understand how ketogenic food products affect oxygen toxicity in undersea divers. Oxygen toxicity affecting the central nervous system, mainly the brain, is a result of breathing higher than normal oxygen levels at elevated pressures as can be seen in SCUBA diving or inside a hyperbaric (pressure) chamber. This is a condition that may cause a wide variety of symptoms such as: vision disturbances, ear-ringing, nausea, twitching, irritability, dizziness, and potentially loss of consciousness or seizure. Because nutritional ketosis has been used to reduce or eliminate seizures in humans, it may be beneficial to reduce oxygen toxicity as well. The investigators hope this study will provide a help to develop practical and useful methods for improving the safety of undersea Navy divers, warfighters and submariners.
    Detailed Description
    Central nervous system (CNS) oxygen toxicity continues to be a risk for military divers and constrains their operations. Manifestations of this condition range from nausea, twitching, and tinnitus to seizures and unresponsiveness, and the latter may lead to death by drowning. The NAVY has a need for better methods to prevent or delay the onset of CNS oxygen toxicity (CNSOT) and to safely expand the scope of diving operations. It is the broad objective of this study to generate information that will enhance warfighter safety and performance in relevant NAVY operations by reducing the risk of CNS oxygen toxicity. It is known that nutritional ketosis through a diet with a high fat-to-carbohydrate ratio (ketogenic diet) can reduce the frequency and severity of epileptic seizures in humans, and a recent animal study has shown that dietary ketosis also delays the onset of CNSOT. In recent years, ketone ester food products ketone esters have been made commercially available which may elevate circulating ketone levels. The investigators aim to investigate whether ketosis from commercially available ketogenic food products prior to a dive will delay the onset of CNSOT. The first aim of this study will be to determine the effect of ketone food product ingestion on serum ketone levels, and document any relevant side effects. Post-ingestion ketone levels will be trended for 3 different ketone food product regimens in 15 total subjects. Data will be used to select the optimal ketone food product strategy to investigate in the second aim. This second aim will be to evaluate the primary hypothesis, that pre-dive ketone food products will prolong latency to CNSOT. To assess this, 20 subjects will be studied in a randomized, controlled, double-blind, crossover methodology. After consuming either the ketone food product or placebo, each subject will complete an immersed, head out hyperbaric oxygen exposure while exercising on an underwater cycle ergometer at 2.06 ATA (35 fsw) until oxygen toxicity symptoms develop or the maximum time limit of 120 minutes is reached. The experiment will be repeated on a different day by each subject after consuming the opposite (ketone food products or placebo). Primary outcome will be time to manifestation of CNSOT. Physiologic monitoring throughout the study will provide secondary endpoints such as cognitive performance, sympathetic nervous system stimulation via electrodermal activity, electroencephalography, cardiorespiratory measures and end-tidal CO2/O2/N2; all adding to our understanding of CNSOT physiology which may guide future mitigation and monitoring strategies.

    6. Conditions and Keywords

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

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Experimental: Ketogenic food products
    Arm Type
    Experimental
    Arm Description
    Dietary Supplement: Ketogenic food products Participants will be given a ketogenic food product prior to the hyperbaric oxygen exposure.
    Arm Title
    Control: Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Dietary Supplement comparator
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Ketogenic food products
    Intervention Description
    Participants will be given a ketogenic food product prior to the hyperbaric oxygen exposure.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Control: Placebo
    Intervention Description
    Participants will be given a dietary supplement comparator prior to the hyperbaric oxygen exposure.
    Primary Outcome Measure Information:
    Title
    Latency to central nervous system oxygen toxicity (CNSOT)
    Description
    Assessment of latency to CNSOT in a simulated working dive breathing 100% oxygen at 2.06 ATA, immersed in water (head out), in a hyperbaric chamber while performing exercise. Endpoint is time to development of signs or symptoms of CNSOT. Maximum duration 120 minutes.
    Time Frame
    2 hours
    Secondary Outcome Measure Information:
    Title
    Cognitive performance
    Description
    Changes in Multi Attribute Test battery scores prior to and during hyperbaric exposure. Tracking score pixel distance from target center, scale min = 0, no defined maximum.
    Time Frame
    Day 1
    Title
    Level of nutritional ketosis as detected by serume beta hydroxybutyrate levels
    Description
    Measure serume beta hydroxybutyrate levels in blood samples
    Time Frame
    Day 1
    Title
    Number of participants with change in EEG
    Description
    Changes in visual EEG inspection prior to and during hyperbaric exposure.
    Time Frame
    Day 1
    Title
    Change in qEEG alpha/delta power ratio (ratio of power in alpha frequency band to power in delta frequency band)
    Description
    Changes in qEEG readings prior to and during hyperbaric exposure
    Time Frame
    Day 1
    Title
    Change in end-tidal CO2
    Description
    Changes in end-tidal CO2 levels in blood samples prior to and during hyperbaric exposure
    Time Frame
    Day 1
    Title
    Change in venous CO2
    Description
    Changes in CO2 levels in blood samples prior to and during hyperbaric exposure
    Time Frame
    Day 1
    Title
    Change in heart rate
    Description
    Changes in heart rate prior to and during hyperbaric exposure
    Time Frame
    Day 1
    Title
    Change in ventilatory rate
    Description
    Changes in ventilatory rate prior to and during hyperbaric exposure
    Time Frame
    Day 1
    Title
    Number of participants who develop CNS oxygen toxicity
    Description
    Any symptoms of CNSOT during hyperbaric exposure as described by participants will be recorded.
    Time Frame
    Day 1

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    39 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Males & females between 18 and 39 years old. Measured (Phase 2) VO2max ≥ 30 ml/kg/min (female) or 35 ml/kg/min (male). BMI ≤ 30.0 unless VO2max and baseline exercise profile is deemed appropriate for the study by the PI. (Phase 2 only) Able to exercise continuously on cycle ergometer for 2 hours. (Phase 2 only) Able to equalize middle ears and tolerate hyperbaric chamber exposure test. Exclusion Criteria: Prolonged QTc on initial ECG Currently pregnant or attempting to become pregnant. Have a medical history of: Smoking history deemed significant by PI Known significant electrolyte disorders Coronary artery disease Cardiac arrhythmia deemed significant by PI Lung disease Hypertension Seizures Exercise intolerance or inability to meet inclusion requirements Psychiatric disorder deemed significant by PI Previous pneumothorax or pneumomediastinum Hypo- or hyperglycemia Diabetes Inability to equalize middle ear spaces during hyperbaric compression Claustrophobia Regularly take any medications which may alter heart rate, blood pressure, neurotransmitter function, alter seizure threshold, mood or affect per PI discretion. Any other condition limiting ability to perform exercise testing or dive profile as determined by the investigators.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Bruce Derrick, MD
    Phone
    919-684-5537
    Email
    bruce.derrick@duke.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Abha Singh
    Phone
    919-668-8700
    Email
    abha.singh@duke.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bruce Derrick, MD
    Organizational Affiliation
    Duke Health
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Effects of Pre-dive Ketone Food Products on Latency to CNS Oxygen Toxicity (Aim 2)

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