Thermogenesis
Conditions
Keywords
brown adipose tissue, beta2-adrenergic agonist, cold exposure
Brief summary
The purpose of the study is to asses brown adipose tissue activity in humans after intravenous administration of the selective beta-2-adrenergic agonist fenoterol as compared to the natural activator of brown adipose tissue, a mild cold stimulus.
Detailed description
The activation of brown adipose tissue in response to beta-2-adrenergic stimulation as compared to cold exposure will be studied in an open-label, cross-over trial in healthy volunteers with random sequence of the two study interventions a) and b): 1. A bolus of 25µg fenoterol will be slowly injected intravenously during 2-3 minutes followed by a continuous infusion of fenoterol 1µg/min over 120 minutes. The total dose of fenoterol per subject will thus be 145µg. 2. During 120 minutes participants will be exposed to a mild cold stimulus water using cooling sleeves, covering the participant's waist, is gradually decrease body surface temperature to 10 degrees or to the lowest tolerable temperature without shivering. Energy expenditure will be measured during both interventions by indirect calorimetry and brown adipose tissue activity will determined by 18F-FDG-PET/CT 30 min after injection of 75 MBq of 18F-FDG.
Interventions
DRUGFenoterol
Intravenous infusion
OTHERMild cold exposure
Body surface cooling
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Open-label, 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 18,5-23 kg/m2 or 30-35 kg/m2
Exclusion criteria
* History or signs of any medical or psychological condition * pregnancy or lactation * medications except prescription free analgesics and contraceptives * habitual alcohol or tobacco use * weight change \>5% within prior 3 months * Resting heart rate \>85 bpm * Systolic blood pressure \>140 mmHg or diastolic blood pressure \<50 mmHg * Presence of following ECG changes: ST-segment deviations, QTc \>500ms, signs of pre-excitation * Hyper- or Hypothyroidism * inability to follow study procedures * Enrolment of the investigator, his/her family members, employees and other dependent persons * hypersensitivity to cold * enrolment into study with ionizing radiation within prior 12 months. * Cold induced thermogenesis of less than 5% basal metabolic rate and normal weight or cold induced thermogenesis of more than 5% and overweight (determined during screening visit)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BAT SUVmean | 30 minutes after end of intervention | 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 | maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0) |
| BAT Volume | 30 minutes after intervention | volume of supraclavicular adipose tissue (according to BARCIST 1.0) |
| BAT glycolytic volume | 30 minutes after intervention | volume of supraclavicular adipose tissue x SUVmean (according to BARCIST 1.0) |
| Change in energy expenditure | First and last 30 minutes of intervention | Quantitative change in EE above resting metabolic rate in response to the respective study intervention. Measured by indirect calorimetry. |
Countries
Switzerland
Outcome results
None listed