Ketone Esters for Optimization of Cognitive Performance in Hypoxia

This study will investigate the effects of ketone ester drinks on cognitive performance in hypoxia.

Study Overview

• Status: Unknown
• Conditions: Hypoxia; Ketosis
• Intervention / Treatment: Dietary supplement: Taste Matched Placebo; Other: Hypoxic exposure; Dietary supplement: Ketone Ester

Detailed Description

In the setting of altitude-induced hypoxia, cognitive capacity degrades and can compromise both individual and team performance. This degradation is linked to falling brain energy (ATP) levels and an increased reliance on anaerobic energy production from glucose. Ketone bodies are the evolutionary alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies (ketosis) maintains brain ATP levels and reduce cerebral anaerobic glycolysis during hypoxia. Ketosis can be achieved when fasting or following a ketogenic diet; however, these approaches are impractical. Exogenous ketone ester supplementation allows for rapid (< 30 mins) and significant elevation of blood ketone levels without the need to maintain a diet or fast.

HVMN, in collaboration with researchers at IHMC, proposes a study to investigate the effects of consuming an FDA-approved ketone ester 'food' on cognitive performance in the setting of hypoxia. For the proposed 4-arm within-subject study, participants will complete a cognitive performance test battery under the conditions of normoxia and then hypoxia following consumption of a ketone ester drink or a placebo drink (N.B for each study drink cognitive performance in both hypoxia and normoxia will be assessed in ONE visit):

VISIT A:

Arm1: Normoxia + Placebo Arm 2: Hypoxia + Placebo

VISIT B:

Arm 3: Normoxia + Ketone ester Arm 4: Hypoxia + Ketone ester

The investigators hypothesize that ketone ester supplementation will attenuate hypoxia-induced deterioration of operator cognitive performance.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

* Pass medical examination on enrollment.

Exclusion Criteria:

* Active smoker, substance abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Normoxia; Taste, volume and appearance matched drink given before cognitive testing in normoxia	Dietary supplement: Taste Matched Placebo; Placebo that tastes similar to active intervention
Placebo Comparator: Placebo + Hypoxia; Taste, volume and appearance matched drink given before cognitive testing in hypoxia	Dietary supplement: Taste Matched Placebo; Placebo that tastes similar to active intervention; Other: Hypoxic exposure; Participants will breath through a mask to provide the amount of oxygen typically seen at 16-17,000ft of altitude.
Experimental: Ketone Ester + Normoxia; Ketone ester drink given before cognitive testing in normoxia	Dietary supplement: Ketone Ester; Flavored sports drink containing deltaG (betahydroxybutyrate monoester) as the sole active ingredient, diluted with water.; Other Names: HVMN Ketone
Experimental: Ketone Ester + Hypoxia; Ketone ester drink given before cognitive testing in hypoxia	Other: Hypoxic exposure; Participants will breath through a mask to provide the amount of oxygen typically seen at 16-17,000ft of altitude.; Dietary supplement: Ketone Ester; Flavored sports drink containing deltaG (betahydroxybutyrate monoester) as the sole active ingredient, diluted with water.; Other Names: HVMN Ketone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive Performance- Visual Acuity	Cognitive performance (visual acuity) will be assessed using the RightEye testing system (https://www.righteye.com).	Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.
Change in Cognitive Performance- Contrast Sensitivity	Cognitive performance (contrast sensitivity) will be assessed using the RightEye testing system (https://www.righteye.com).	Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.
Change in Cognitive Performance- Choice Reaction Time	Cognitive performance (choice reaction time) will be assessed using both the RightEye testing system (https://www.righteye.com) and the DANA testing system (http://www.danabrainvital.com).	Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.
Change in Cognitive Performance- Eye Tracking- Smooth Pursuit	Cognitive performance (eye tracking) will be assessed by looking for smooth pursuit (horizontal and vertical) using the RightEye testing system (https://www.righteye.com).	Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.
Change in Cognitive Performance- Eye Tracking- Saccades	Cognitive performance (eye tracking) will be assessed by looking at saccade speed (horizontal and vertical) using the RightEye testing system (https://www.righteye.com).	Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.
Change in Cognitive Performance- Simple Reaction Time	Cognitive performance (simple reaction time) will be assessed using both the RightEye testing system (https://www.righteye.com) and the DANA testing system (http://www.danabrainvital.com).	Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Grip Strength	Grip strength will be measured using a	Measured 3 times (baseline [time = 0 min], after normoxia [60 min post study drink 1] and after hypoxia [60 min post study drink 2]) in each of the two test visits.
Change in blood ketone levels	Blood ketone levels will be measured in a finger prick blood samples using a clinical grade, handheld glucose/ketone meter (Abott Diabetes Care).	Measured 5 times at regular intervals through each of the two study visits. [time (min) = 0, 30, 75, 105, 150]
Change in blood glucose levels	Blood glucose levels will be measured in a finger prick blood samples using a clinical grade, handheld glucose/ketone meter (Abott Diabetes Care).	Measured 5 times at regular intervals through each of the two study visits. [time (min) = 0, 30, 75, 105, 150]

Collaborators and Investigators

• Sponsor: HVMN Inc
• Collaborators: Florida Institute for Human and Machine Cognition

Publications and helpful links

General Publications

• Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017.
• Suzuki M, Suzuki M, Sato K, Dohi S, Sato T, Matsuura A, Hiraide A. Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats. Jpn J Pharmacol. 2001 Oct;87(2):143-50. doi: 10.1254/jjp.87.143.
• Kirsch JR, D'Alecy LG, Mongroo PB. Butanediol induced ketosis increases tolerance to hypoxia in the mouse. Stroke. 1980 Sep-Oct;11(5):506-13. doi: 10.1161/01.str.11.5.506.
• Xu K, Sun X, Eroku BO, Tsipis CP, Puchowicz MA, LaManna JC. Diet-induced ketosis improves cognitive performance in aged rats. Adv Exp Med Biol. 2010;662:71-5. doi: 10.1007/978-1-4419-1241-1_9.

Helpful Links

• HVMN product website

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2018
• Primary Completion (Anticipated): October 31, 2018
• Study Completion (Anticipated): November 15, 2018

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 6, 2018
• Last Update Submitted That Met QC Criteria: September 5, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: KEHYPOX18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No