Brown Adipose Tissue (BAT) Physiology, Cold Exposure
Conditions
Brief summary
The purpose of the study is to asses brown adipose tissue activity after a cold mild stimulus, preceded by 200mg caffeine or placebo administration.
Detailed description
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.
Interventions
single dose of 200mg caffeine orally in study visit A
DRUGPlacebo
single dose of 1 tablet Placebo in study visit B
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, placebo-controlled cross-over trial in healthy volunteers with random sequence of the two study interventions.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 18.5 to 25 kg/m2 * Able to give informed consent as documented by signature * Moderate caffeine consumption (1 to 3 cups of coffee per day) * Increase of EE in response to mild cold of ≥ 5% of REE
Exclusion criteria
* Known hypersensitivity or allergy to caffeine * Concomitant medication other than prescription free analgesics (paracetamol and NSAID) and oral contraceptives * Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, cardiac arrhythmia, hypertension, diabetes mellitus, hyper- or hypothyroidism) * History of depressive disorder or anxiety disorder * Smoker / habitual tobacco use * Habitual excessive alcohol use * Regular consumption of caffeine containing energy drinks * Weight change of \>5% within 3 months prior to inclusion * Systolic blood pressure \>140 mmHg and/or diastolic blood pressure \> 95 mmHg. * Resting heart rate \>90 bpm * Hypersensitivity to cold (e.g. Raynaud syndrome) * Known or suspected non-compliance, drug or alcohol abuse * Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant. * Enrolment of the investigator, his/her family members, employees, and other dependent persons * Enrolment into another study using ionizing radiation within the previous 12 months. * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BAT SUVmean | 30 minutes after end of intervention in study visit A and B. | Description: 18F-FDG uptake into the supra-clavicular brown adipose tissue as determined by 18F-FDG PET-CT after the respective study intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BAT SUVmax | 30 minutes after intervention in study visit A and B. | maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0) as determined by 18F-FDG PET-CT after the respective study intervention |
| BAT Volume | 30 minutes after intervention in study visit A and B. | volume of supraclavicular adipose tissue (according to BARCIST 1.0) as determined by 18F-FDG PET-CT after the respective study intervention. |
| Cold induced thermogenesis (CIT) | immediately after the intervention (caffeine or placebo) | rise in energy expenditure above baseline occurring during mild cold exposure in the respective study intervention. |
| Resting energy expenditure (REE) | immediately after the intervention (caffeine or placebo) | REE during warm conditions and at the end of cold exposure. |
| Respiratory exchange ratio (RER): | immediately after the intervention (caffeine or placebo) | Ratio between carbon dioxide production and oxygen consumption (VCO2/VO2) during the enregy expenditure (EE) measurements. |
| Skin temperature | immediately after the intervention (caffeine or placebo) | 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 |
| Metabolom and Lipidome profile | immediately after the intervention (caffeine or placebo) | Plasma metabolome and lipidome profiles. |
| Caffeine and its metabolites | immediately after the intervention (caffeine or placebo) | Plasma caffeine and its metabolites. |
Countries
Switzerland
Contacts
CONTACTMatthias Betz, Prof.
CONTACTJaël Senn, MD
PRINCIPAL_INVESTIGATORMatthias Betz, Prof.
University Hospital, Basel, Switzerland
Outcome results
None listed