To develop and validate an in vivo magnetic resonance method to track 13C-labeled fatty acids to the liver in healthy subjects.
ID
Source
Brief title
Condition
- Other condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Health condition
insuline resistentie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Determination of the lowest dose that allows for sufficient signal to noise
ratio and the time of maximal 13C accumulation in liver). Detection and
quantification of fractional enrichment (FE) of accumulated 13C-labelled lipids
in liver at different time points after dietary intake.
Secondary outcome
• Total- and 13C-enriched blood plasma levels of FFA, triglycerides,
glucose.
Background summary
Fat accumulation in liver is strongly associated with insulin resistance and
therefore a major determinant of metabolic health. Very little is known about
the dietary factors that determine fat content in this tissue in humans, which
is mainly due to the inaccessibility of this organ for human studies. However,
using non-invasive imaging techniques, fat accumulation and metabolism can be
studied in ectopic fat stores. Particularly interesting in the field of food
and nutrition is the application of 13C magnetic resonance spectroscopy (MRS)
to follow the time-course of retention of dietary fat in human tissues in *real-
time*.
Study objective
To develop and validate an in vivo magnetic resonance method to track
13C-labeled fatty acids to the liver in healthy subjects.
Study design
The fractional enrichment of 13C in fatty acids will be detected by MRS at
various time-points up to 24 hrs after consumption of a breakfast containing
13C-enriched algal fat.
Subjects will come to the hospital three times:
• First visit: includes a medical history and a physical activity questionnaire
and a measurement of height and body weight and a hydrostatic measurement to
measure body composition.
• Second visit: the subjects have to report to the hospital after an overnight
fast at 7:00u. A baseline MRS-scan for 13C enrichment of intracellular lipid
quantification in the liver (duration ca 60 min) will be performed. Immediately
after the baseline measurements (ca. 8:00h), a blood sample will be taken.
Subsequently, a standardized breakfast will be given, containing 13C-labeled
algal fat (breakfast will contain 40% of average daily energy requirements,
composition: 30% of energy as fat, 10% as proteins and 60% as carbohydrates. In
total, 6 bloodsamples will be collected (at t = 0,1, 2.5, 4, 5.5 and 7h) and 5
MRS measurements will be performed that day (final scan ends around 15:00h). A
dinner (40% of daily energy requirement, normal energy composition) will be
given to the subject to be consumed at home.
• Third visit: at 7:00h a final MRI/MRS measurement in the liver will be
performed (again after an overnight fast).
Intervention
The subjects have to consume several standardised meals, including a breakfast
with 13C labeled fatty acids. They have to visit the hospital three times in
fasted state. Several MRS scans and bloodsamples will be taken. Additionally,
a medical questionnaire has to be filled in.
Study burden and risks
The experimental procedures are without significant risks. MRS is a safe
procedure (no ionizing radiation), with no known health risk as long as none of
the exclusion criteria is met. There is a chance that MRI reveals an unexpected
medical condition, of which the subject will be informed. His/her physician
will also be informed.
To track fatty acids from the diet, the subjects will consume lipids that are
enriched in 13C. Uptake and metabolism of 13C lipids are identical to naturally
abundant lipids. 13C is a stable isotope (no radiation), that is occurring in
our natural environment (with a natural abundance of 1.1%). A GMP-certified
pharmacy (Radboud Nijmegen UMC) will prepare the 13C enriched algal mixture in
capsules.
P. Debyelaan 25
Maastricht 6202 AZ
NL
P. Debyelaan 25
Maastricht 6202 AZ
NL
Listed location countries
Age
Inclusion criteria
Lean subjects (study 1):
- Age 18-65 years
- Normal BMI 18-25 kg/m2
- Stable dietary habits
- Generally healthy, no medication use;Obese subjects (study2)
- Age 18-65 years,
- Obese, BMI 30-35 kg/m2
- Stable dietary habits (no weight-reducing diet last year)
- Generally healthy, no medication use
Exclusion criteria
Persons that have any of the following will be excluded from the study:
- Any medical condition requiring treatment and/or medication use
- Alcohol consumption of more than 20 g per day (± 2 units) or other drug abuse
- Unstable body weight (weight gain or loss > 3 kg in the past three months)
- Contraindications for MRI scan:
• Aneurysm clips
• Implanted neural stimulator
• Implanted cardiac pacemaker of defibrillator
• Cochlear implant
• Iron- containing corpora aliena in the eye or brain
• Artificial (heart) valves which is contraindicated for MRI
• Claustrophobia
- Subjects, who do not want to be informed about unexpected medical findings, or do not wish that their treating physician is informed.
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 |
|---|---|
| CCMO | NL38120.068.12 |
| Other | wordt na goedkeuring geregistreerd via 'clinical trial.gov |