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Completed

NCT Number: NCT06217159

Mechanistic Effect of Ketones on Cerebral Blood Flow

Oral supplements containing exogenous ketones have recently become available and represent a novel tool for increasing plasma ketone bodies without the need for dietary restriction. Early evidence suggests that oral ketone supplements may enhance cerebral blood flow (CBF). However, a higher dose of a ketone monoester has been shown to slightly lower blood pH and reduce end-tidal CO2 (PetCO2) due to compensatory hyperventilation, which is accompanied by parallel reductions in CBF. Whether reductions in PetCO2 causes reductions in CBF is currently unknown.

The purpose of this study is to investigate the effect of manipulating PetCO2 at normocapnia (PetCO2 maintained at baseline) or poikilocapnia (no PetCO2 targeting; breathing room air), following the ingestion of a dose of a ketone monoester on CBF and cerebrovascular reactivity to CO2 in young adults.

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Key information

Conditions

Cerebrovascular Function Cerebral Blood Flow

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Having a normal blood pressure (≤125/≤85 mmHg)
  • Between the ages of 18 and 35

Exclusion criteria

  • Individuals who are obese (body mass index > 30 kg/m^2)
  • Individuals who smoke
  • Individuals with respiratory illnesses
  • A history of type 2 diabetes, hypoglycemia, or cardiovascular diseases (i.e. heart attack, stroke)
  • Individuals currently following a ketogenic diet or taking ketone supplements
  • Individuals with a history of concussion(s) with persistent symptoms
  • Individuals participating in elite-level physical training (i.e. varsity athletics)

Treatment and study plan

Poikilocapnia

Dietary Supplement

Following ingestion of 0.6 g β-OHB/kg body weight ketone monoester, participants will wear a specialized face mask and breathe room air for 60 min. The face mask will be attached to an automated gas-blender system; however, only room air will be delivered.

Normocapnia

Dietary Supplement

Following ingestion of 0.6 g β-OHB/kg body weight ketone monoester, participants will be outfitted with a specialized face mask and breathe air with a slightly higher concentration of CO2 to maintain PetCO2 to resting baseline values for 60 min. Gas will be continuously delivered by an automated gas-blender system.

Primary outcomes

  1. Resting cerebral blood flow (CBF)

    Time frame: 90-minutes

    Measured via duplex ultrasound of the internal carotid artery and vertebral artery

Secondary outcomes

  1. Plasma beta-hydroxybutyrate area under the curve

    Time frame: 90-minutes

    Venous blood samples will be obtained via intravenous catheter

  2. Blood pH

    Time frame: 90-minutes

    Venous blood samples will be obtained via intravenous catheter

  3. End-tidal CO2

    Time frame: 90-minutes

    Breath-by-breath analysis performed via RespirAct (RespirAct, Thornhill Research, Toronto, ON, Canada).

  4. Mean arterial pressure (MAP)

    Time frame: 90-minutes

    Automated blood pressure cuff measurements of brachial artery pressure in mmHg

  5. Cerebrovascular Reactivity of the Internal Carotid and Middle Cerebral Artery as assessed by Duplex Ultrasound and Transcranial Doppler Ultrasound, respectively.

    Time frame: 90-minutes

    Automated gas-blender used to apply sequential gas delivery using an algorithm to target end-tidal CO2 at +3mmHg, +6mmHg, and +9mmHg above baseline, using five-minute step-wise stages. Simultaneously, changes in cerebral blood flow in the internal carotid artery and the middle cerebral artery will be assessed using duplex ultrasound and transcranial Doppler ultrasound, respectively. The final minute of each stage will be analyzed to characterize the slope of cerebrovascular reactivity to CO2 in the internal carotid artery and the middle cerebral artery.

  6. Middle Cerebral Artery Blood Velocity

    Time frame: 90-minutes

    Measured via transcranial Doppler Ultrasound using a 2MHz probe

Sponsors and collaborators

Lead sponsor

McMaster University

Other

Registry information

Official study title

The Mechanistic Effect of Ketones on Cerebral Blood Flow and Cerebrovascular Function

Acronym: MEKC

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Jan 22, 2024
Registry last updated
Apr 23, 2025

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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