Brain Insulin SensitivityNCT06395051
Effects of Ketone Monoesters on Brain Function
A study testing Ketone Monoester in people with Brain Insulin Sensitivity and Brain Vascular Function, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Disturbances in brain insulin-sensitivity are not only observed in obesity and type 2 diabetes (T2D), but also during brain aging and in dementia. Ketone monoester supplements may improve brain insulin-sensitivity, which can be quantified by measuring the gray-matter cerebral blood flow (CBF) response to intranasally… Read more about this study
- Who is it for?
- Ages 60 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Brain Insulin Sensitivity, Brain Vascular Function, Cerebral Blood Flow
- What is being tested?
- Ketone Monoester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 Jul 2024to 15 Nov 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 60 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men, aged between 60-75 years
- BMI between 25-30 kg/m2
- Fasting plasma glucose < 7.0 mmol/L
- Fasting serum TC < 8.0 mmol/L
- Fasting serum TAG < 4.5 mmol/L
- Systolic blood pressure < 160 mmHg and diastolic blood pressure < 100 mmHg
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- Stable body weight (weight gain or loss < 3 kg in the past three months)
- Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
- No difficult venipuncture as evidenced during the screening visit
Who cannot join
- Women
- Left-handedness
- Following a low-carbohydrate diet or consuming nutritional ketone supplements
- Current smoker, or smoking cessation < 12 months
- Diabetic patients
- Familial hypercholesterolemia
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- Abuse of drugs
- More than 3 alcoholic consumptions per day
- Use of products or dietary supplements known to interfere with the main outcomes as judged by the principal investigators
- Use medication to treat blood pressure, lipid or glucose metabolism, or neurological or mental disorders.
- Use of an investigational product within another biomedical intervention trial within the previous 1-month
- Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
- Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
- Contra-indications for MRI imaging (e.g. pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia).
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg
About this study
Official title: Acute Effects of Ketone Monoester Supplementation on Brain Function in Older Men with Overweight
Disturbances in brain insulin-sensitivity are not only observed in obesity and type 2 diabetes (T2D), but also during brain aging and in dementia. Ketone monoester supplements may improve brain insulin-sensitivity, which can be quantified by measuring the gray-matter cerebral blood flow (CBF) response to intranasally administered insulin. We hypothesize that acute ketone monoester supplementation increases (regional) brain vascular function and insulin-sensitivity thereby improving cognitive performance and appetite control. The primary objective is to evaluate in older men the acute effect of ketone monoester supplementation on (regional) brain vascular function and insulin-sensitivity, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labelling (ASL). The CBF response to intranasal insulin is a robust and sensitive physiological marker of brain insulin-sensitivity. Secondary objectives are to investigate effects on cognitive performance as assessed with a neuropsychological test battery, and appetite control as quantified by functional MRI (fMRI) with visual food cues.
- Conditions
- Brain Insulin Sensitivity, Brain Vascular Function, Cerebral Blood Flow, Cognitive Performance, Appetite Control
- Being tested
- Ketone Monoester, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone MonoesterDietary supplement
Ketone monoester supplement (395 mg/kg body mass)
PlaceboDietary supplement
The placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Ketone monoesters Receives: Dietary Supplement: Ketone Monoester |
| Placebo | Placebo comparator | Taste- and volume-matched placebo Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain Vascular Function
Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
Measured: Change from placebo intervention at 30 minutes after supplement intake
Brain Insulin Sensitivity
Cerebral blood flow measurements before and after a nasal insulin spray as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
Measured: Change from placebo intervention at 60 minutes after supplement intake
Secondary outcomes (11)
Appetite-related brain reward activity
Blood oxygenation level-dependent (BOLD)-functional MRI (fMRI) response to food cues
Measured: Change from placebo intervention at 40 minutes after supplement intake
Cognitive Performance
Cambridge Neuropsychological Test Automated Battery (CANTAB)
Measured: Change from placebo intervention at 120 minutes after supplement intake
Brain Perfusion
Transcranial Doppler (TCD) ultrasound will be used to assess the velocity of blood flow through the middle cerebral artery (MCA)
Measured: Change from placebo intervention at 120 minutes after supplement intake
Blood pressure
Office blood pressure and heart rate
Measured: Change from placebo intervention at 90 minutes after supplement intake
Ketone metabolism
Circulating beta-hydroxybutyrate concentrations
Measured: During 120 minutes following supplement intake
Glucose metabolism
Circulating glucose and insulin concentrations
Measured: During 120 minutes following supplement intake
Markers related to low-grade systemic inflammation
Circulating high-sensitive C-reactive protein concentrations
Measured: During 120 minutes following supplement intake
Appetite hormones
Circulating ghrelin concentrations
Measured: During 120 minutes following supplement intake
Perceived hunger and satiety
Visual analogue scale (VAS) questionnaires
Measured: During 120 minutes following supplement intake
Anthropometric measurements
Weight, length, waist and hip circumference
Measured: Before supplement intake
Food intake
Food Frequency Questionnaire to assess food intake over the past month
Measured: Once 120 minutes following supplement intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2024
- Study start3 Jul 2024
- Primary completion15 Nov 2024
- Study completion15 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Insulin SensitivityStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Study participants will receive in random order acutely 395 mg/kg body weight ketone monoesters or placebo, seperated by a wash-out period of at least 1 week.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter J Joris, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06395051
- Sponsor's protocol ID
- METC24-008
- Status last verified
- Feb 2025
- First submitted
- 29 Apr 2024
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Ketone Monoester Supplementation on Brain Function in Older Men with Overweight
- ClinicalTrials.gov ID
- NCT06395051
- Acronym / sponsor ID
- METC24-008
- Conditions
- Brain Insulin Sensitivity, Brain Vascular Function, Cerebral Blood Flow, Cognitive Performance, Appetite Control
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 3 Jul 2024 (actual)
- Primary completion
- 15 Nov 2024 (actual)
- Study completion
- 15 Nov 2024 (actual)
- First posted
- 1 May 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.
Disturbances in brain insulin-sensitivity are not only observed in obesity and type 2 diabetes (T2D), but also during brain aging and in dementia. Ketone monoester supplements may improve brain insulin-sensitivity, which can be quantified by measuring the gray-matter cerebral blood flow (CBF) response to intranasally administered insulin. We hypothesize that acute ketone monoester supplementation increases (regional) brain vascular function and insulin-sensitivity thereby improving cognitive performance and appetite control. The primary objective is to evaluate in older men the acute effect of ketone monoester supplementation on (regional) brain vascular function and insulin-sensitivity, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labelling (ASL). The CBF response to intranasal insulin is a robust and sensitive physiological marker of brain insulin-sensitivity. Secondary objectives are to investigate effects on cognitive performance as assessed with a neuropsychological test battery, and appetite control as quantified by functional MRI (fMRI) with visual food cues.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Study participants will receive in random order acutely 395 mg/kg body weight ketone monoesters or placebo, seperated by a wash-out period of at least 1 week.
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Dietary Supplement: Ketone MonoesterKetone monoesters |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboTaste- and volume-matched placebo |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Men, aged between 60-75 years
- BMI between 25-30 kg/m2
- Fasting plasma glucose < 7.0 mmol/L
- Fasting serum TC < 8.0 mmol/L
- Fasting serum TAG < 4.5 mmol/L
Key exclusion criteria (14 listed)
- Women
- Left-handedness
- Following a low-carbohydrate diet or consuming nutritional ketone supplements
- Current smoker, or smoking cessation < 12 months
- Diabetic patients
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 |
|---|---|---|
| Ketone MonoesterKetone monoester supplement (395 mg/kg body mass) | Dietary supplement | Experimental |
| PlaceboThe placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water | Dietary supplement | Placebo |
Primary outcome
Brain Vascular Function
Time frame: Change from placebo intervention at 30 minutes after supplement intake
Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
Brain Insulin Sensitivity
Time frame: Change from placebo intervention at 60 minutes after supplement intake
Cerebral blood flow measurements before and after a nasal insulin spray as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
11 secondary outcomes
Appetite-related brain reward activity
Time frame: Change from placebo intervention at 40 minutes after supplement intake
Cognitive Performance
Time frame: Change from placebo intervention at 120 minutes after supplement intake
Brain Perfusion
Time frame: Change from placebo intervention at 120 minutes after supplement intake
Blood pressure
Time frame: Change from placebo intervention at 90 minutes after supplement intake
Ketone metabolism
Time frame: During 120 minutes following supplement intake
Glucose metabolism
Time frame: During 120 minutes following supplement intake
Markers related to low-grade systemic inflammation
Time frame: During 120 minutes following supplement intake
Appetite hormones
Time frame: During 120 minutes following supplement intake
Perceived hunger and satiety
Time frame: During 120 minutes following supplement intake
Anthropometric measurements
Time frame: Before supplement intake
Food intake
Time frame: Once 120 minutes following supplement intake
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 20 Feb 2025.
- Individual participant dataSharing planned: No
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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.
Peter J Joris, PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone Monoester in people with Brain Insulin Sensitivity and Brain Vascular Function, run by Maastricht University Medical Center at 1 site in Netherlands.
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 9 inclusion and 14 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 20 Feb 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 Netherlands. 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?
Brain Vascular Function (time frame: Change from placebo intervention at 30 minutes after supplement intake). The study lists 2 primary outcomes in all. 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 20 Feb 2025.