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

NCT ID: NCT05831228

Last Updated: 2025-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2025-03-31

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.

Conditions

Oxygen Toxicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Experimental: Ketogenic food products

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

Group Type: EXPERIMENTAL

Ketogenic food products

Intervention Type: DIETARY_SUPPLEMENT

Participants will be given a ketogenic food product prior to the hyperbaric oxygen exposure.

Control: Placebo

Dietary Supplement comparator

Group Type: PLACEBO_COMPARATOR

Control: Placebo

Intervention Type: DIETARY_SUPPLEMENT

Participants will be given a dietary supplement comparator prior to the hyperbaric oxygen exposure.

Interventions

Ketogenic food products

Participants will be given a ketogenic food product prior to the hyperbaric oxygen exposure.

Intervention Type: DIETARY_SUPPLEMENT

Control: Placebo

Participants will be given a dietary supplement comparator prior to the hyperbaric oxygen exposure.

Intervention Type: DIETARY_SUPPLEMENT

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:

1. Smoking history deemed significant by PI

2. Known significant electrolyte disorders

3. Coronary artery disease

4. Cardiac arrhythmia deemed significant by PI

5. Lung disease

6. Hypertension

7. Seizures

8. Exercise intolerance or inability to meet inclusion requirements

9. Psychiatric disorder deemed significant by PI

10. Previous pneumothorax or pneumomediastinum

11. Hypo- or hyperglycemia

12. Diabetes

13. Inability to equalize middle ear spaces during hyperbaric compression

14. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

United States Navy

FED

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce Derrick, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

Duke University Hospital

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

Pro00111000_1

Identifier Type: -

Identifier Source: org_study_id