Mechanistic Effect of Ketones on Cerebral Blood Flow

Cerebral Blood Flow Clinical Trial

— MEKC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06217159
• Other study ID #: MEKC
• Status: Recruiting
• Phase: N/A
• Start date: January 19, 2024
• Est. completion date: August 31, 2024

Study information

• Verified date: January 2024
• Source: McMaster University
• Contact: Jeremy J Walsh, PhD
• Phone: 9055259140
• Email: walshj18[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 31, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cerebral Blood Flow
• Cerebrovascular Function

Intervention

Dietary Supplement:
• Poikilocapnia
Following ingestion of 0.6 g ß-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
Following ingestion of 0.6 g ß-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.

Locations

Country	Name	City	State
Canada	McMaster University	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resting cerebral blood flow (CBF)	Measured via duplex ultrasound of the internal carotid artery and vertebral artery	90-minutes
Secondary	Plasma beta-hydroxybutyrate area under the curve	Venous blood samples will be obtained via intravenous catheter	90-minutes
Secondary	Blood pH	Venous blood samples will be obtained via intravenous catheter	90-minutes
Secondary	End-tidal CO2	Breath-by-breath analysis performed via RespirAct (RespirAct, Thornhill Research, Toronto, ON, Canada).	90-minutes
Secondary	Mean arterial pressure (MAP)	Automated blood pressure cuff measurements of brachial artery pressure in mmHg	90-minutes
Secondary	Cerebrovascular Reactivity of the Internal Carotid and Middle Cerebral Artery as assessed by Duplex Ultrasound and Transcranial Doppler Ultrasound, respectively.	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.	90-minutes
Secondary	Middle Cerebral Artery Blood Velocity	Measured via transcranial Doppler Ultrasound using a 2MHz probe	90-minutes