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)-…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Structural brain disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the acute effect of ketone monoesters as compared with
placebo on (regional) brain vascular function and insulin-sensitivity, as
assessed by the gray-matter CBF response to intranasally administered insulin
using MRI ASL.
Secondary outcome
Secondary endpoints are the acute effects of ketone monoesters as compared with
placebo on cognitive performance, as assessed with a neuropsychological test
battery (CANTAB), and appetite-related brain reward activity, as quantified by
the blood oxygenation level-dependent (BOLD)-fMRI response to food cues.
Background 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.
Study objective
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 design
This intervention study will have a randomized, double-blind,
placebo-controlled crossover trial. The two test days will be separated by a
washout period of at least one week.
Intervention
Participants will receive in random order 395 mg/kg body weight of a ketone
monoester supplement ((R)-3-hydroxybutyl-(R)-3-hydroxybutyrate) or a
taste-matched placebo, separated by a wash-out period of at least 1 week.
Study burden and risks
Participants will be screened to determine eligibility during one visit of 30
minutes. During these screening visits, anthropometric measurements will be
performed and blood pressure will be determined. In addition, a fasting blood
sample (5.5 mL) will be drawn. During the testing days, participants will
receive a drink with ketone monoesters or placebo. Both supplements are safe
and no side effects related to the supplement are expected. During both testing
days, measurements will be performed and blood will be sampled (a total of
137.5 mL during the whole trial). During these tests, participants must visit
the university and are not allowed to eat. Some participants may report pain
during placement of an intravenous cannula. ASL perfusion MRI non-invasively
records CBF without any significant risks. Measurements will be performed on a
Siemens 3.0 Tesla Magnetom Prisma Fit scanner. No contrast medication or
radioactive tracer substance will be administered to the participants. Brain
insulin-sensitivity will be assessed by quantifying acute effects of insulin as
nasal spray on CBF, which is safe and has already been used in multiple studies
within our department without side effects. Other measurements are routine and
are not expected to lead to physical side effects. Participants that not fully
adhere to the study protocol will be excluded from the statistical analyses,
because a per protocol analysis will be performed. The total time investment,
excluding travelling time, is approximately 9 hours. The study will provide
insight into the potential beneficial effects of ketone monoesters on brain
insulin-sensitivity in older men with overweight.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
- Men, aged between 60-75 years
- BMI between 25-30 kg/m2
- Fasting plasma glucose < 7.0 mmol/L
- Fasting serum total cholesterol < 8.0 mmol/L
- Fasting serum triacylglycerol < 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).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT06395051 |
| CCMO | NL86460.068.24 |