The purpose of the study is to asses brown adipose tissue activity after a cold mild stimulus, preceded by 200mg caffeine or placebo administration.
Brown adipose tissue (BAT) activation is typically through beta3-adrenoceptors (beta3-AR), but beta3-alone are less efficacious than cold in activating human BAT. Recent research suggests that adenosine, released during cold exposure, plays a key role in BAT thermogenesis. This study aims to investigate the role of the adenosine A2A receptor (A2AR) in BAT activation through a randomized trial with mild cold exposure and caffeine, a potent A2AR antagonist, to explore new therapeutic strategies for metabolic diseases. This is a randomized, double-blind, placebo-controlled cross-over trial involving healthy volunteers. The study includes a screening visit and two main study visits (A and B), which will occur in random order. During the two study visits, resting energy expenditure will be assessed by indirect calorimetry under warm conditions and following mild cold exposure, after administration of either caffeine or placebo. For cold exposure, participants will wear cooling sleeves around the waist, which gradually lower the surface body temperature to 10°C or to the lowest tolerable temperature without inducing shivering. Additionally, BAT activity will be assessed using 18F-FDG PET/CT, performed 30 minutes after the injection of 75 MBq of 18F-FDG.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
12
single dose of 200mg caffeine orally in study visit A
single dose of 1 tablet Placebo in study visit B
University Hospital Basel, Department of Endocrinology
Basel, Switzerland
RECRUITINGBAT SUVmean
Description: 18F-FDG uptake into the supra-clavicular brown adipose tissue as determined by 18F-FDG PET-CT after the respective study intervention
Time frame: 30 minutes after end of intervention in study visit A and B.
BAT SUVmax
maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0) as determined by 18F-FDG PET-CT after the respective study intervention
Time frame: 30 minutes after intervention in study visit A and B.
BAT Volume
volume of supraclavicular adipose tissue (according to BARCIST 1.0) as determined by 18F-FDG PET-CT after the respective study intervention.
Time frame: 30 minutes after intervention in study visit A and B.
Cold induced thermogenesis (CIT)
rise in energy expenditure above baseline occurring during mild cold exposure in the respective study intervention.
Time frame: immediately after the intervention (caffeine or placebo)
Resting energy expenditure (REE)
REE during warm conditions and at the end of cold exposure.
Time frame: immediately after the intervention (caffeine or placebo)
Respiratory exchange ratio (RER):
Ratio between carbon dioxide production and oxygen consumption (VCO2/VO2) during the enregy expenditure (EE) measurements.
Time frame: immediately after the intervention (caffeine or placebo)
Skin temperature
Changes in skin temperature after mild cold stimulus. It will be measured during the hole study visits during warm condition and after cold stimulation, using wireless temperature sensors (iButton Thermochron) attached to the skin at 11 pre-defined locations
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Time frame: immediately after the intervention (caffeine or placebo)
Metabolom and Lipidome profile
Plasma metabolome and lipidome profiles.
Time frame: immediately after the intervention (caffeine or placebo)
Caffeine and its metabolites
Plasma caffeine and its metabolites.
Time frame: immediately after the intervention (caffeine or placebo)