Cerebrovascular FunctionkCBFNCT06032156
Ketone Dose and Cerebral Blood Flow Study
A study testing Low Dose β-OHB and High Dose β-OHB in people with Cerebrovascular Function and Cognition, run by McMaster University at 1 site in Canada.
Trial summary
Ketone bodies are produced by the liver during periods of food scarcity or severe carbohydrate restriction. Blood ketones are an alternative fuel source used by the brain, heart, and skeletal muscle during periods of fasting. 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, Cognition
- What is being tested?
- Low Dose β-OHB and High Dose β-OHB
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 8 Nov 2023to 30 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
- Between the ages of 18 and 35
Who cannot join
- Presence of obesity (body mass index > 30 kg/m^2)
- Presence of known cardiovascular disease
- Presence of type 2 diabetes
- History of cardiovascular events requiring hospitalization (i.e., heart attack)
- History of concussion(s) with persistent symptoms
- Currently following a ketogenic diet and/or taking ketone body supplements
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Acute Effects of a High Versus Low Dose of a Ketone Monoester Supplement on Cerebral Blood Flow and Cognition
Ketone bodies are produced by the liver during periods of food scarcity or severe carbohydrate restriction. Blood ketones are an alternative fuel source used by the brain, heart, and skeletal muscle during periods of fasting. Further, ketones bodies act as a signalling molecule that have pleiotropic effects that upregulate cellular stress-resistance pathways throughout the body.
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 and improve cognition. However, the dose-dependent effects of a single ketone supplement on cerebral blood flow and cognition in young adults is currently unknown.
Read more
The purpose of this study is to characterize the effects of ingesting a high versus low dose of an oral ketone monoester on cerebral blood flow, circulating blood markers, and cognition in young adults.
As an exploratory aim, this study will investigate how oxygen uptake kinetics during submaximal exercise are impacted 2 hours after ingestion of a ketone supplement. Recent findings indicate that ketone supplementation may impair exercise performance due to the physiological stress (i.e., pH disturbances) imposed by an acute ketone dose. Delaying exercise onset by 2 hours after ingestion of a ketone supplement may enhance oxygen kinetics in a dose-dependent manner.
- Conditions
- Cerebrovascular Function, Cognition
- Being tested
- Low Dose β-OHB, High Dose β-OHB, Placebo
- Keywords
- Cerebral Blood Flow, Cognition, Beta-hydroxybutyrate (β-OHB)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose β-OHBDietary supplement
Ingestion of a low dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.3 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
High Dose β-OHBDietary supplement
Ingestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
PlaceboOther
Ingestion of a taste-matched calorie-free placebo drink followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Single dose of a taste-matched calorie-free placebo Receives: Other: Placebo |
| High Dose β-OHB | Experimental | Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight) Receives: Dietary Supplement: High Dose β-OHB |
| Low Dose β-OHB | Experimental | Single dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight) Receives: Dietary Supplement: Low Dose β-OHB |
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 extra-cranial arteries (internal carotid and vertebral arteries).
Measured: 2-hour
Secondary outcomes (6)
Cognitive Function
The MST (Mnemonic Similarity Task) will be used to assess hippocampal-dependent memory and pattern separation.
Measured: 2-hour
Plasma beta-hydroxybutyrate area under the curve
Venous blood samples will be obtained via intravenous catheter
Measured: 2-hour
Brain-derived neurotrophic factor (BDNF)
Serum and plasma BDNF measured in venous blood samples will be obtained via intravenous catheter
Measured: 2-hour, then following completion of submaximal exercise bout
Oxygen uptake (VO2)
Breath-by-breath analysis performed via metabolic cart
Measured: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
End-tidal CO2
Breath-by-breath analysis performed via PowerLab Gas Analyzer (AD Instruments)
Measured: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
Mean arterial pressure (MAP)
Automated blood pressure cuff measurement of brachial artery pressure in mmHg.
Measured: 2-hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2023
- Study start8 Nov 2023
- Primary completion30 May 2024
- Study completion30 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular FunctionStudies of the same condition, open and under way.
- 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 double-blind placebo-controlled crossover design will be used to test 3 conditions. Participants will consume 60 mL of a supplement containing: 1) a low β-OHB dose (0.3g/kg) body weight of the ketone monoester; \[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate); 2) a high β-OHB dose (0.6g/kg body weight); or 3) a taste-matched calorie-free inert placebo drink.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeremy J Walsh, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06032156
- Sponsor's protocol ID
- kCBF
- Acronym
- kCBF
- Status last verified
- Dec 2023
- First submitted
- 6 Apr 2023
- Last updated
- 13 Feb 2026
- 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
Publications
Rourke AJ, Yong CMS, Coombs GB, Odisho AR, Nash JA, Bone J, Al-Khazraji BK, Walsh JJ. Acute ketone monoester ingestion lowers resting cerebral blood flow: a randomized cross-over trial. J Physiol. 2026 Mar;604(6):2525-2541. doi: 10.1113/JP287320. Epub 2025 May 11.
PubMed 40349325
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Acute Effects of a High Versus Low Dose of a Ketone Monoester Supplement on Cerebral Blood Flow and Cognition
- ClinicalTrials.gov ID
- NCT06032156
- Acronym / sponsor ID
- kCBF / kCBF
- Conditions
- Cerebrovascular Function, Cognition
- Keywords
- Cerebral Blood Flow, Cognition, Beta-hydroxybutyrate (β-OHB)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- 8 Nov 2023 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 30 Aug 2024 (actual)
- First posted
- 11 Sep 2023 (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.
Ketone bodies are produced by the liver during periods of food scarcity or severe carbohydrate restriction. Blood ketones are an alternative fuel source used by the brain, heart, and skeletal muscle during periods of fasting. Further, ketones bodies act as a signalling molecule that have pleiotropic effects that upregulate cellular stress-resistance pathways throughout the body.
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 and improve cognition. However, the dose-dependent effects of a single ketone supplement on cerebral blood flow and cognition in young adults is currently unknown.
The purpose of this study is to characterize the effects of ingesting a high versus low dose of an oral ketone monoester on cerebral blood flow, circulating blood markers, and cognition in young adults.
As an exploratory aim, this study will investigate how oxygen uptake kinetics during submaximal exercise are impacted 2 hours after ingestion of a ketone supplement. Recent findings indicate that ketone supplementation may impair exercise performance due to the physiological stress (i.e., pH disturbances) imposed by an acute ketone dose. Delaying exercise onset by 2 hours after ingestion of a ketone supplement may enhance oxygen kinetics in a dose-dependent manner.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- A randomized double-blind placebo-controlled crossover design will be used to test 3 conditions. Participants will consume 60 mL of a supplement containing: 1) a low β-OHB dose (0.3g/kg) body weight of the ketone monoester; [R]-3-hydroxybutyl [R]-3-hydroxybutyrate); 2) a high β-OHB dose (0.6g/kg body weight); or 3) a taste-matched calorie-free inert placebo drink.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboSingle dose of a taste-matched calorie-free placebo |
| High Dose β-OHB | Experimental | Dietary Supplement: High Dose β-OHBSingle dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.6 g β-OHB/kg body weight) |
| Low Dose β-OHB | Experimental | Dietary Supplement: Low Dose β-OHBSingle dose of a ketone monoester ([R]-3-hydroxybutyl [R]-3-hydroxybutyrate; 0.3 g β-OHB/kg body weight) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Between the ages of 18 and 35
Key exclusion criteria (6 listed)
- Presence of obesity (body mass index > 30 kg/m^2)
- Presence of known cardiovascular disease
- Presence of type 2 diabetes
- History of cardiovascular events requiring hospitalization (i.e., heart attack)
- History of concussion(s) with persistent symptoms
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 |
|---|---|---|
| Low Dose β-OHBIngestion of a low dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.3 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures. | Dietary supplement | Low Dose β-OHB |
| High Dose β-OHBIngestion of a high dose [R]-3-hydroxybutyl [R]-3-hydroxybutyrate (0.6 g β-OHB/kg body weight) followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures. | Dietary supplement | High Dose β-OHB |
| PlaceboIngestion of a taste-matched calorie-free placebo drink followed by 2-hours of rest. Submaximal exercise to be performed following 2-hour resting measures. | Other | Placebo |
Primary outcome
Resting cerebral blood flow (CBF)
Time frame: 2-hour
Measured via duplex ultrasound of the extra-cranial arteries (internal carotid and vertebral arteries).
6 secondary outcomes
Cognitive Function
Time frame: 2-hour
Plasma beta-hydroxybutyrate area under the curve
Time frame: 2-hour
Brain-derived neurotrophic factor (BDNF)
Time frame: 2-hour, then following completion of submaximal exercise bout
Oxygen uptake (VO2)
Time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
End-tidal CO2
Time frame: 2-hour, then during submaximal exercise (performed after 2-hour rest period)
Mean arterial pressure (MAP)
Time frame: 2-hour
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 13 Feb 2026.
- Derived from this study: PubMed 40349325Rourke AJ, Yong CMS, Coombs GB, Odisho AR, Nash JA, Bone J, Al-Khazraji BK, Walsh JJ. Acute ketone monoester ingestion lowers resting cerebral blood flow: a randomized cross-over trial. J Physiol. 2026 Mar;604(6):2525-2541. doi: 10.1113/JP287320. Epub 2025 May 11.
- 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 Low Dose β-OHB and High Dose β-OHB in people with Cerebrovascular Function and Cognition, 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 1 inclusion and 6 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 13 Feb 2026. 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: 2-hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06032156, which also lists 1 linked publication.
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 13 Feb 2026.