- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06395051
Effects of Ketone Monoesters on Brain Function
April 29, 2024 updated by: Maastricht University Medical Center
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.
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
18
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Kevin MR Nijssen
- Phone Number: +31433881305
- Email: k.nijssen@maastrichtuniversity.nl
Study Contact Backup
- Name: Peter J Joris
- Phone Number: +31883887250
- Email: p.joris@maastrichtuniversity.nl
Study Locations
-
-
Limburg
-
Maastricht, Limburg, Netherlands
- Maastricht University Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- Women
- Left-handedness
- Following a low-carbohydrate diet or consuming nutritional ketone supplements
- Current smoker, or smoking cessation < 12 months
- Diabetic patients
- Familial hypercholesterolemia
- 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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Experimental
Ketone monoesters
|
Ketone monoester supplement (395 mg/kg body mass)
|
Placebo Comparator: Placebo
Taste- and volume-matched placebo
|
The placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
Change from placebo intervention at 30 minutes after supplement intake
|
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)
|
Change from placebo intervention at 60 minutes after supplement intake
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Appetite-related brain reward activity
Time Frame: Change from placebo intervention at 40 minutes after supplement intake
|
Blood oxygenation level-dependent (BOLD)-functional MRI (fMRI) response to food cues
|
Change from placebo intervention at 40 minutes after supplement intake
|
Cognitive Performance
Time Frame: Change from placebo intervention at 120 minutes after supplement intake
|
Cambridge Neuropsychological Test Automated Battery (CANTAB)
|
Change from placebo intervention at 120 minutes after supplement intake
|
Brain Perfusion
Time Frame: Change from placebo intervention at 120 minutes after supplement intake
|
Transcranial Doppler (TCD) ultrasound will be used to assess the velocity of blood flow through the middle cerebral artery (MCA)
|
Change from placebo intervention at 120 minutes after supplement intake
|
Blood pressure
Time Frame: Change from placebo intervention at 90 minutes after supplement intake
|
Office blood pressure and heart rate
|
Change from placebo intervention at 90 minutes after supplement intake
|
Ketone metabolism
Time Frame: During 120 minutes following supplement intake
|
Circulating beta-hydroxybutyrate concentrations
|
During 120 minutes following supplement intake
|
Glucose metabolism
Time Frame: During 120 minutes following supplement intake
|
Circulating glucose and insulin concentrations
|
During 120 minutes following supplement intake
|
Markers related to low-grade systemic inflammation
Time Frame: During 120 minutes following supplement intake
|
Circulating high-sensitive C-reactive protein concentrations
|
During 120 minutes following supplement intake
|
Appetite hormones
Time Frame: During 120 minutes following supplement intake
|
Circulating ghrelin concentrations
|
During 120 minutes following supplement intake
|
Perceived hunger and satiety
Time Frame: During 120 minutes following supplement intake
|
Visual analogue scale (VAS) questionnaires
|
During 120 minutes following supplement intake
|
Anthropometric measurements
Time Frame: Before supplement intake
|
Weight, length, waist and hip circumference
|
Before supplement intake
|
Food intake
Time Frame: Once 120 minutes following supplement intake
|
Food Frequency Questionnaire to assess food intake over the past month
|
Once 120 minutes following supplement intake
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Peter J Joris, Maastricht University Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
July 1, 2024
Primary Completion (Estimated)
March 31, 2025
Study Completion (Estimated)
March 31, 2025
Study Registration Dates
First Submitted
April 29, 2024
First Submitted That Met QC Criteria
April 29, 2024
First Posted (Actual)
May 1, 2024
Study Record Updates
Last Update Posted (Actual)
May 1, 2024
Last Update Submitted That Met QC Criteria
April 29, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- METC24-008
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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