Effects of Ketone Monoesters on Brain Function

NCT06395051 | Completed

• 1 other identifier: METC24-008
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (11)

• Appetite-related brain reward activity

  Change from placebo intervention at 40 minutes after supplement intake

• Cognitive Performance

  Change from placebo intervention at 120 minutes after supplement intake

• Brain Perfusion

  Change from placebo intervention at 120 minutes after supplement intake

• Blood pressure

  Change from placebo intervention at 90 minutes after supplement intake

• Ketone metabolism

  During 120 minutes following supplement intake

Study Arms (2)

Experimental

EXPERIMENTAL

Ketone monoesters

Dietary Supplement: Ketone Monoester

Placebo

PLACEBO COMPARATOR

Taste- and volume-matched placebo

Dietary Supplement: Placebo

Interventions

Ketone Monoester DIETARY_SUPPLEMENT

Ketone monoester supplement (395 mg/kg body mass)

Experimental

Placebo DIETARY_SUPPLEMENT

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

Placebo

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Location

Study Officials

• Peter J Joris, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 1, 2024
• Study Start: July 3, 2024
• Primary Completion: November 15, 2024
• Study Completion: November 15, 2024
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)