Effects of Ketone Monoesters on Brain Function

Cognitive Performance Clinical Trial

Official title:

Acute Effects of Ketone Monoester Supplementation on Brain Function in Older Men With Overweight

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06395051
• Other study ID #: METC24-008
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: March 31, 2025

Study information

• Verified date: April 2024
• Source: Maastricht University Medical Center
• Contact: Kevin MR Nijssen
• Phone: +31433881305
• Email: k.nijssen[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 60 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Appetite Control
• Brain Vascular Function
• Cerebral Blood Flow
• Cognitive Performance
• Insulin Resistance

Intervention

Dietary Supplement:
• Ketone Monoester
Ketone monoester supplement (395 mg/kg body mass)
• Placebo
The placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain Vascular Function	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
Primary	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)	Change from placebo intervention at 60 minutes after supplement intake
Secondary	Appetite-related brain reward activity	Blood oxygenation level-dependent (BOLD)-functional MRI (fMRI) response to food cues	Change from placebo intervention at 40 minutes after supplement intake
Secondary	Cognitive Performance	Cambridge Neuropsychological Test Automated Battery (CANTAB)	Change from placebo intervention at 120 minutes after supplement intake
Secondary	Brain Perfusion	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
Secondary	Blood pressure	Office blood pressure and heart rate	Change from placebo intervention at 90 minutes after supplement intake
Secondary	Ketone metabolism	Circulating beta-hydroxybutyrate concentrations	During 120 minutes following supplement intake
Secondary	Glucose metabolism	Circulating glucose and insulin concentrations	During 120 minutes following supplement intake
Secondary	Markers related to low-grade systemic inflammation	Circulating high-sensitive C-reactive protein concentrations	During 120 minutes following supplement intake
Secondary	Appetite hormones	Circulating ghrelin concentrations	During 120 minutes following supplement intake
Secondary	Perceived hunger and satiety	Visual analogue scale (VAS) questionnaires	During 120 minutes following supplement intake
Secondary	Anthropometric measurements	Weight, length, waist and hip circumference	Before supplement intake
Secondary	Food intake	Food Frequency Questionnaire to assess food intake over the past month	Once 120 minutes following supplement intake