The primary objective of this intervention study is to examine in abdominally obese men the acute effect of inorganic nitrate as compared with placebo on brain insulin-sensitivity, as assessed by the gray-matter CBF response to intranasally…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the acute effect of inorganic nitrate as compared with
placebo on the acute effect of inorganic nitrate as compared with placebo on
brain 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 inorganic nitrate as compared with
a placebo on brain vascular function, as assessed by CBF. Additionally, the
effect of brain insulin-sensitivity changes on cognitive performance in the
domain of executive function and spatial memory will be investigated using
CANTAB, after consumption of nitrate as compared with placebo
Background summary
Disturbances in brain insulin-sensitivity are not only observed in abdominal
obesity and type 2 diabetes mellitus (T2D), but also during brain aging and in
dementia. Inorganic nitrate may improve brain insulin-sensitivity, which can be
quantified by measuring the gray-matter cerebral blood flow (CBF) response to
intranasally administered insulin, through beneficial effects on brain vascular
function. Therefore, we now hypothesize that inorganic nitrate, which can be
found in several vegetables such as beetroot, improves brain
insulin-sensitivity, as assessed by the gray-matter CBF response to
intranasally administered insulin, in abdominally obese men.
Study objective
The primary objective of this intervention study is to examine in abdominally
obese men the acute effect of inorganic nitrate as compared with placebo on
brain insulin-sensitivity, as assessed by the gray-matter CBF response to
intranasally administered insulin using magnetic resonance imaging (MRI)
technique Arterial Spin Labelling (ASL). Secondary objective is to investigate
the acute effects of inorganic nitrate as compared with a placebo on brain
vascular function. Additionally, the effect of brain insulin-sensitivity
changes on cognitive performance in the domain of executive function and
spatial memory will be investigated using the Cambridge Neuropsychological Test
Automated Battery (CANTAB), after consumption of nitrate as compared with
placebo. Finally, effects on the more conventional cardiometabolic risk
markers, such as blood pressure and fasting and postprandial glucose and lipid
metabolism, will be investigated as exploratory outcomes.
Study design
The study will have a randomized, controlled, double-blinded, cross-over
design. The two test days will be separated by a washout period of at least one
week.
Intervention
During each test day, participants will receive a drink with potassium nitrate
(KNO3) providing a total of 10 mmol (625 mg) of inorganic nitrate or an
isomolar solution of potassium chloride (KCl) as placebo in random order.
Study burden and risks
Participants will be screened to determine eligibility during one visit of 30
minutes. During these screening visits, we will measure anthropometrics and
blood pressure (BP) will be determined. Additionally, a venous blood sample (8
mL) will be drawn. During the testing days, participants will receive a drink
with KNO3 or KCl as placebo. Both supplements are safe and no expected side
effects related to the supplement are expected. During both testing days
measurements will be performed and blood will be sampled (a total of 228 mL
during the whole trial). During these tests, participants have to visit the
university and are not allowed to eat. Some study 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 is already used in a study from our
department. 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 inorganic nitrate on brain insulin-sensitivity in
abdominally obese men.
Universiteitsingel 50
Maastricht 6229 ER
NL
Universiteitsingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
- Men
- Aged between 18 - 60 years
- Waist circumference minimal 102 cm (abdominally obese)
- Fasting plasma glucose * 7.0 mmol/L
- Fasting serum total cholesterol * 8.0 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
- Willingness not to use antibacterial mouth wash or toothpaste, chewing-gum
and tongue-scraping a week before the study
- No difficult venipuncture as evidenced during the screening visit
Exclusion criteria
- Women
- Left-handedness
- 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
- Pharmacological treatment advised based on the Dutch general practitioners
association (NHG) for cardiovascular risk management.
- 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
- Specific contra-indications for MRI imaging, including pacemakers,
surgical clips/material in body, metal splinters in eye, claustrophobia, or
tattoos in the facial area, such as permanent make-up.
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 | NCT@@@@(wordtpasverkregennagoedkeuringMETC) |
| CCMO | NL75164.068.20 |