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NCT Number: NCT07051655

The Effects of Exogenous Ketones on Cognitive Function

The purpose of this study is to evaluate the acute effects of exogenous ketone monoester (KME) supplementation on cognitive function in three groups of adults aged 19-55 years: (1) obese, sedentary individuals; (2) lean, sedentary individuals; and (3) lean individuals who engage in regular physical activity (e.g., collegiate or amateur athletes). The main questions it aims to answer are to:

* Assess the effects of acute KME supplementation versus placebo on cognitive, sensorimotor, and functional outcomes within groups. * Compare cognitive performance across the three groups.

The primary outcome is cognitive performance assessed using the NIH Toolbox Cognition Battery. Secondary Outcomes include sensorimotor performance, measured using the Senaptec Sensory System, and driving performance, assessed with a driving simulator.

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Key information

Conditions

Placebo - Control Ketone Monoester

Age range

19 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

The purpose of this study is to evaluate the acute effects of exogenous ketone monoester (KME) supplementation on cognitive function in three groups of adults aged 19-55 years: (1) obese, sedentary individuals; (2) lean, sedentary individuals; and (3) lean individuals who engage in regular physical activity (e.g., collegiate or amateur athletes).

Exogenous ketones are considered a functional food, providing potential health benefits beyond basic nutrition. Specifically, KME has been shown to elevate circulating β-hydroxybutyrate (βHB), an alternative brain fuel that may enhance cognitive performance. Prior studies have demonstrated that KME improves cognition in individuals with Alzheimer's disease and mild cognitive impairment; however, its effects in otherwise healthy, sedentary individuals-particularly those with obesity-or in physically active individuals remain unknown.

Emerging evidence suggests that individuals with obesity may exhibit early cognitive deficits, especially in executive function and processing speed, which could increase their risk of accelerated cognitive decline with aging. These deficits may be partially attributed to impaired cerebral glucose metabolism. Since ketones serve as an efficient alternative energy substrate for the brain, ketone supplementation may help compensate for these metabolic deficits and enhance cognitive performance.

This study aims to compare cognitive performance across the three groups and assess the effects of acute KME supplementation versus placebo on cognitive, sensorimotor, and functional outcomes. The primary outcome is cognitive performance assessed using the NIH Toolbox Cognition Battery. Secondary Outcomes include sensorimotor performance, measured using the Senaptec Sensory System, and driving performance, assessed with a driving simulator.

This three-group design allows for the investigation of differential responses to ketone supplementation across a spectrum of metabolic health and physical conditioning. By using sensitive, multimodal assessment tools, this study will help determine whether exogenous ketones confer cognitive and functional benefits broadly, or whether these effects are most pronounced in metabolically impaired populations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 19-55 years
  • BMI 30-40 (obese group) or 18-25 (lean and athlete groups)
  • Sedentary status (<2 hrs/week of structured physical activity) for obese and lean groups
  • Active athlete status (≥5 days/week of structured activity) for athlete group

Exclusion criteria

  • Diagnosed neurological conditions (e.g., Parkinson's disease, multiple sclerosis, schizophrenia, muscular dystrophy, stroke, cerebral palsy)
  • History of seizures
  • Use of medications for diabetes, mood disorders, or attention disorders
  • Pregnant or breastfeeding
  • Current or recent use (within 1 month) of exogenous ketone supplements or adherence to a ketogenic diet

Treatment and study plan

Ketone Monoester (KE)

Dietary Supplement

Participants will undergo two test days separated by 3-7 days. On both test days, participants will arrive fasted and consume a single dose of ketone monoester or placebo (357 mg/kg of body weight) in random order. Drinks will be prepared by non-study personnel and matched in taste, texture, and appearance to maintain blinding. Thirty minutes after consuming the ketone monoester or placebo, cognitive assessments will be completed including NIH Toolbox cognitive assessments, Senaptec Sensory Station, and driving simulation.

Other names: ketone monoester (KME)

Placebo

Dietary Supplement

Participants will undergo two test days separated by 3-7 days. On one test day, participants will consume a single dose of placebo (357 mg/kg of body weight). Thirty minutes after consuming the placebo, cognitive assessments will be completed including NIH Toolbox cognitive assessments, Senaptec Sensory Station, and driving simulation.

Primary outcomes

  1. NIH Toolbox Cognition Battery Composite Score and Domain-Specific Subtests - Executive function

    Time frame: Test Day 1 and Test Day 2

    Cognitive function will be assessed using the NIH Toolbox Cognition Battery, administered on an iPad.

    • Dimensional Change Card Sort Test - Measures executive function and cognitive flexibility by assessing the ability to switch between mental rules.

  2. NIH Toolbox Cognition Battery Composite Score and Domain-Specific Subtests - Attention

    Time frame: Test Day 1 and Test Day 2

    Cognitive function will be assessed using the NIH Toolbox Cognition Battery, administered on an iPad.

    • Flanker Inhibitory Control and Attention Test - Evaluates attention and the ability to inhibit responses to distracting information.

  3. NIH Toolbox Cognition Battery Composite Score and Domain-Specific Subtests - Processing Speed

    Time frame: Test Day 1 and Test Day 2

    Cognitive function will be assessed using the NIH Toolbox Cognition Battery, administered on an iPad.

    • Oral Symbol Digit Substitution Test - Assesses processing speed by requiring participants to match symbols and digits under time pressure.

  4. NIH Toolbox Cognition Battery Composite Score and Domain-Specific Subtests - Memory

    Time frame: Test Day 1 and Test Day 2

    Cognitive function will be assessed using the NIH Toolbox Cognition Battery, administered on an iPad.

    • Picture Sequence Memory Test - Tests episodic memory by having participants recall sequences of illustrated scenes in the correct order.

Secondary outcomes

  1. Senaptec Sensory Station - Visual Acuity

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station. This includes:

    Visual Clarity Test - Measures the sharpness of vision using high-contrast letters; similar to a Snellen chart.

  2. Senaptec Sensory Station - Visual perception

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Contrast Sensitivity - Assesses ability to detect subtle differences in luminance; important in low-light or low-contrast environments.

  3. Senaptec Sensory Station - Stereopsis, spatial awareness

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Depth Perception - Measures the ability to judge the relative distance between objects using binocular vision.

  4. Senaptec Sensory Station - Oculomotor control

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Near-Far Quickness - Assesses speed and accuracy in shifting focus between near and far objects; linked to accommodative and vergence flexibility.

  5. Senaptec Sensory Station - Visual search

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Target Capture - tests speed and accuracy in identifying and responding to a target among distractors.

  6. Senaptec Sensory Station - Visual working memory

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Perception Span - Evaluates ability to recall the location and identity of briefly presented visual stimuli.

  7. Senaptec Sensory Station - Attention

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Go/No-Go - Assesses impulse control by requiring responses to specific stimuli while inhibiting others

  8. Senaptec Sensory Station - Processing Speed

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Reaction Time - Measures the speed of motor response to a visual stimulus; includes both simple and choice RT.

  9. Senaptec Sensory Station - Visual Tracking

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Multiple Object Tracking - Requires simultaneous tracking of multiple moving targets among distractors

  10. Senaptec Sensory Station - Visuomotor Integration

    Time frame: Test Day 1 and Test Day 2

    Participants will complete the full suite of visual and sensorimotor evaluations within the "Evaluation" tab of the Senaptec Sensory Station.

    Eye-Hand Coordination - Measures the ability to synchronize visual input with precise hand movement.

  11. Driving Simulator Performance Metrics - Attention

    Time frame: Test Day 1 and Test Day 2

    Cognitive and functional performance will be assessed using a high-fidelity driving simulator.

    • Lane-keeping variability

    Driving simulator data will provide an ecologically valid, real-world proxy of cognitive-motor integration and decision-making under time pressure.

  12. Driving Simulator Performance Metrics - Reaction Time

    Time frame: Test Day 1 and Test Day 2

    Cognitive and functional performance will be assessed using a high-fidelity driving simulator. Participants will complete a standardized driving task

    • Mean reaction time to unexpected events (e.g., pedestrian crossing)
    • Braking accuracy and response latency

    Driving simulator data will provide an ecologically valid, real-world proxy of cognitive-motor integration and decision-making under time pressure.

Study contacts

Contact information is provided by the study sponsor or research team.

Eric Plaisance

CONTACT

[email protected]

Sarah K Sweatt, PhD

CONTACT

[email protected]

205-975-5398

Sponsors and collaborators

Lead sponsor

University of Alabama at Birmingham

Other

Registry information

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jul 4, 2025
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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