Clinical trial NCT06217159: Mechanistic Effect of Ketones on Cerebral Blood Flow
Official title: The Mechanistic Effect of Ketones on Cerebral Blood Flow and Cerebrovascular Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cerebrovascular Function
Cerebral Blood Flow
Keywords: Cerebral Blood Flow
Beta-hydroxybutyrate (β-OHB)
Cerebrovascular Function
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2024-01-22
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A randomized single-blind crossover design will be used to test 2 conditions. Participants will consume 60 mL of a supplement containing 0.6g/kg body weight of the ketone monoester (\[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate) in both conditions, and their PetCO2 will be maintained in the normocapnic conditions or not maintained in the poikilocapnic condition, in a randomized order.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Resting cerebral blood flow (CBF)
timeFrame: 90-minutes
Secondary outcomes:
measure: Plasma beta-hydroxybutyrate area under the curve
timeFrame: 90-minutes
measure: Blood pH
timeFrame: 90-minutes
measure: End-tidal CO2
timeFrame: 90-minutes
measure: Mean arterial pressure (MAP)
timeFrame: 90-minutes
measure: Cerebrovascular Reactivity of the Internal Carotid and Middle Cerebral Artery as assessed by Duplex Ultrasound and Transcranial Doppler Ultrasound, respectively.
timeFrame: 90-minutes
measure: Middle Cerebral Artery Blood Velocity
timeFrame: 90-minutes
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Jeremy J Walsh, PhD
role: PRINCIPAL_INVESTIGATOR
References: