Clinical trial NCT06395051: Effects of Ketone Monoesters on Brain Function
Official title: Acute Effects of Ketone Monoester Supplementation on Brain Function in Older Men with Overweight
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Insulin Sensitivity
Brain Vascular Function
Cerebral Blood Flow
Cognitive Performance
Appetite Control
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2024-05-01
Enrollment: 18
Sex: MALE
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: PREVENTION

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.


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).

Primary outcomes:
measure: Brain Vascular Function
timeFrame: Change from placebo intervention at 30 minutes after supplement intake
measure: Brain Insulin Sensitivity
timeFrame: Change from placebo intervention at 60 minutes after supplement intake
Secondary outcomes:
measure: Appetite-related brain reward activity
timeFrame: Change from placebo intervention at 40 minutes after supplement intake
measure: Cognitive Performance
timeFrame: Change from placebo intervention at 120 minutes after supplement intake
measure: Brain Perfusion
timeFrame: Change from placebo intervention at 120 minutes after supplement intake
measure: Blood pressure
timeFrame: Change from placebo intervention at 90 minutes after supplement intake
measure: Ketone metabolism
timeFrame: During 120 minutes following supplement intake
measure: Glucose metabolism
timeFrame: During 120 minutes following supplement intake
measure: Markers related to low-grade systemic inflammation
timeFrame: During 120 minutes following supplement intake
measure: Appetite hormones
timeFrame: During 120 minutes following supplement intake
measure: Perceived hunger and satiety
timeFrame: During 120 minutes following supplement intake
measure: Anthropometric measurements
timeFrame: Before supplement intake
measure: Food intake
timeFrame: Once 120 minutes following supplement intake
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: Peter J Joris, PhD
role: PRINCIPAL_INVESTIGATOR
References: