Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02964442 |
Other study ID # |
2015/00715 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
October 23, 2015 |
Est. completion date |
October 24, 2023 |
Study information
Verified date |
May 2024 |
Source |
Clinical Nutrition Research Centre, Singapore |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Brown adipose tissue (BAT) thermogenesis can be assessed by IR thermography, the accompanying
increase metabolic rate can be measured by whole body calorimetry and BAT volume can be
precisely measured by MRI. The aim of the study is to validate IRT for BAT thermogenesis
against the present gold standard 18-FDG-PET scan, quantify BAT volume by fat fraction MRI
and measure the accompanying increase in BMR by whole body calorimetry among healthy
euthyroid subjects.
Description:
It is now known that human adults do possess viable brown fat in quantities that may be
critical for maintenance of a normal basal metabolic rate (BMR) and body weight, dispelling
the myth that BAT is only present during infancy for thermoregulation. There are data
suggesting that obesity is associated with insufficient BAT. So far the only known and
arguably 'gold standard' methodology of BAT imaging in humans is 18-FDG-PET. Yet 18-FDG-PET
imaging has significant limitations, given its restricted spatial resolution and its
non-trivial level of ionizing radiation (2.8 mSv). The International Commission for
Radiological Protection recommends that the radiation exposure for the general public should
not exceed 1mSv/year and 1.5 mSv/year from background radiation. In addition, 18-FDG-PET
depends on glucose uptake by BAT that does not directly measure its key metabolic activity,
namely fatty acid oxidation. Finally, PET scans are very costly. This makes the present gold
standard far from ideal as a research tool for investigating BAT physiology. Thus the first
objective of this project is to develop an alternative activated BAT imaging method that is
not based on ionizing radiation. We are interested in advancing infrared (IR) thermography as
a method to assess BAT activity by developing a novel image processing algorithms for IR
thermography. Much extant literature describes the use of "average temperature" instead of IR
heat flux using the physical principles of radiative heat transfer and thermodynamics to
quantify heat from BAT. Also,IR digital still-shots were mostly employed in the past whereas
none have reported the analysis of IR flux using a video sequence which more accurately
integrates time-varying heat energy output. Without precision in capturing and processing the
rich IR data, the value of IR thermography as a tool for BAT research is limited. It is thus
crucial to convert the IR images into a readout that reflects energy output. We will thus
develop, validate and apply automatic IR image processing with computer software that can
efficiently calculate BAT activation. In this proposal we will also improve and validate
anatomical fat fraction MRI as a tool for evaluating BAT volumes based on the higher water
content in BAT compared with that in WAT. Fat fraction imaging by MRI has been proposed but
no proper validation has been done due to the difficulty in matching PET and MRI data on BAT.
Instead of using pharmacologic agents (e.g. beta 3-adrenergic receptor agonists such as
mirabegron) that can be administered to activate BAT instead of cold stimulus, we will employ
capsiate (i.e. capsinoids - non-spicy analogues of capsaicin in peppers and chilies) that
have been proven to effectively stimulate BAT in thermoneutral conditions as confirmed by PET
scans. We have conducted a preliminary study approved by the DSRB that showed the
effectiveness of capsinoids in stimulating BAT. There are publications documenting the use of
MRI in distinguishing BAT from WAT, each with their advantages and disadvantages. In this
present study, we will perform a proof-of-concept study by simultaneous acquisition of MRI
and 18-FDG-PET in a dual-modality fusion MRI-PET scanner available at the Clinical Imaging
Research Centre (CIRC) to image BAT in humans, and correlate this with IR thermography of the
cervical and supraclavicular regions (SCR) and with metabolic rate accurately measured in a
whole body calorimeter. Whole body calorimetry is the real gold standard to assess BAT
activity by measuring nonshivering thermogenesis. IR has so far been validated against
18-FDG-PET in mice and rodents, but equivalent validation in humans has not been published.
If IR thermography is shown to be equivalent or superior to 18-FDG-PET imaging, it will set a
new gold standard in BAT imaging which will be a boon for study of BAT biology in humans.