Ketone Esters for Optimization of Cognitive Performance in Hypoxia

Study Overview
=================
Brief Summary
-----------------
This study will investigate the effects of ketone ester drinks on cognitive performance in hypoxia.

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.

Official Title
-----------------
Ketone Esters for Optimization of Cognitive Performance in Hypoxia

Conditions
-----------------
Hypoxia, Ketosis

Intervention / Treatment
-----------------
* Dietary Supplement: Ketone Ester
* Dietary Supplement: Taste Matched Placebo
* Other: Hypoxic exposure


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: * Pass medical examination on enrollment. Exclusion Criteria: * Active smoker, substance abuse.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Young healthy adults.
Masking: Double


Arms and Interventions

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

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] |