Cerebrovascular FunctionMEKCNCT06217159
Mechanistic Effect of Ketones on Cerebral Blood Flow
A study testing Poikilocapnia and Normocapnia in people with Cerebrovascular Function and Cerebral Blood Flow, run by McMaster University at 1 site in Canada.
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). Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Cerebrovascular Function, Cerebral Blood Flow
- What is being tested?
- Poikilocapnia and Normocapnia
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteCanada
- Study dates
- 19 Jan 2024to 31 Aug 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Having a normal blood pressure (≤125/≤85 mmHg)
- Between the ages of 18 and 35
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Mechanistic Effect of Ketones on Cerebral Blood Flow and Cerebrovascular Function
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.
- Conditions
- Cerebrovascular Function, Cerebral Blood Flow
- Being tested
- Poikilocapnia, Normocapnia
- Keywords
- Cerebral Blood Flow, Beta-hydroxybutyrate (β-OHB), Cerebrovascular Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PoikilocapniaDietary 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.
NormocapniaDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| Poikilocapnia | Sham comparator | Room air-breathing Receives: Dietary Supplement: Poikilocapnia |
| Normocapnia | Experimental | Breathing air mixture with slightly elevated CO2 to maintain PetCO2 to resting baseline levels Receives: Dietary Supplement: Normocapnia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting cerebral blood flow (CBF)
Measured via duplex ultrasound of the internal carotid artery and vertebral artery
Measured: 90-minutes
Secondary outcomes (6)
Plasma beta-hydroxybutyrate area under the curve
Venous blood samples will be obtained via intravenous catheter
Measured: 90-minutes
Blood pH
Venous blood samples will be obtained via intravenous catheter
Measured: 90-minutes
End-tidal CO2
Breath-by-breath analysis performed via RespirAct (RespirAct, Thornhill Research, Toronto, ON, Canada).
Measured: 90-minutes
Mean arterial pressure (MAP)
Automated blood pressure cuff measurements of brachial artery pressure in mmHg
Measured: 90-minutes
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.
Measured: 90-minutes
Middle Cerebral Artery Blood Velocity
Measured via transcranial Doppler Ultrasound using a 2MHz probe
Measured: 90-minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start19 Jan 2024
- Primary completion30 May 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebrovascular FunctionStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeremy Walsh, McMaster University
- Investigators
- Jeremy J Walsh, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06217159
- Sponsor's protocol ID
- MEKC
- Acronym
- MEKC
- Status last verified
- Apr 2025
- First submitted
- 1 Dec 2023
- Last updated
- 23 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will share individual patient data (de-identified) with researchers upon request.
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Mechanistic Effect of Ketones on Cerebral Blood Flow and Cerebrovascular Function
- ClinicalTrials.gov ID
- NCT06217159
- Acronym / sponsor ID
- MEKC / MEKC
- Conditions
- Cerebrovascular Function, Cerebral Blood Flow
- Keywords
- Cerebral Blood Flow, Beta-hydroxybutyrate (β-OHB), Cerebrovascular Function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 19 Jan 2024 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Poikilocapnia | Sham comparator | Dietary Supplement: PoikilocapniaRoom air-breathing |
| Normocapnia | Experimental | Dietary Supplement: NormocapniaBreathing air mixture with slightly elevated CO2 to maintain PetCO2 to resting baseline levels |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Having a normal blood pressure (≤125/≤85 mmHg)
- Between the ages of 18 and 35
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PoikilocapniaFollowing 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. | Dietary supplement | Poikilocapnia |
| NormocapniaFollowing 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. | Dietary supplement | Normocapnia |
Primary outcome
Resting cerebral blood flow (CBF)
Time frame: 90-minutes
Measured via duplex ultrasound of the internal carotid artery and vertebral artery
6 secondary outcomes
Plasma beta-hydroxybutyrate area under the curve
Time frame: 90-minutes
Blood pH
Time frame: 90-minutes
End-tidal CO2
Time frame: 90-minutes
Mean arterial pressure (MAP)
Time frame: 90-minutes
Cerebrovascular Reactivity of the Internal Carotid and Middle Cerebral Artery as assessed by Duplex Ultrasound and Transcranial Doppler Ultrasound, respectively.
Time frame: 90-minutes
Middle Cerebral Artery Blood Velocity
Time frame: 90-minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
- Individual participant dataSharing planned: Yes. The investigators will share individual patient data (de-identified) with researchers upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy J Walsh, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Poikilocapnia and Normocapnia in people with Cerebrovascular Function and Cerebral Blood Flow, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting cerebral blood flow (CBF) (time frame: 90-minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.