Effects of Ketone Monoesters on Brain Function

NCT ID: NCT06395051

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-03
• Study Completion Date: 2024-11-15

Brief 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.

Conditions

Brain Insulin Sensitivity; Brain Vascular Function; Cerebral Blood Flow; Cognitive Performance; Appetite Control

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Experimental

Ketone monoesters

Group Type: EXPERIMENTAL

Ketone Monoester

Intervention Type: DIETARY_SUPPLEMENT

Ketone monoester supplement (395 mg/kg body mass)

Placebo

Taste- and volume-matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

The placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water

Interventions

Ketone Monoester

Ketone monoester supplement (395 mg/kg body mass)

Intervention Type: DIETARY_SUPPLEMENT

Placebo

The placebo will be taste-matched to the active supplement for bitterness using denatonium benzoate and volume-matched with water

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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).

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter J Joris, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Countries

Netherlands

Other Identifiers

METC24-008

Identifier Type: -

Identifier Source: org_study_id