Beta 2 Adrenergic Stimulation vs Cold Exposure to Activate Human Brown Adipose Tissue

Study Overview
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Brief Summary
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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
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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): 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. 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.

Official Title
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Beta 2 Adrenergic Stimulation vs Cold Exposure to Activate Human Brown Adipose Tissue

Conditions
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Thermogenesis

Intervention / Treatment
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* Drug: Fenoterol
* Other: Mild cold exposure


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Open-label, cross-over trial in healthy volunteers with random sequence of the two study interventions
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal weight<br>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. Mild cold exposure: During 120 minutes the water temperature in cooling sleeves, covering the participant's waist, is gradually decreased to 10 degrees or to the lowest tolerable temperature without shivering. | Drug: Fenoterol<br>* Intravenous infusion<br>* Other names: beta2 adrenoreceptor agonist;Other: Mild cold exposure<br>* Body surface cooling<br>|
| Experimental: Overweight<br>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. Mild cold exposure: During 120 minutes the water temperature in cooling sleeves, covering the participant's waist, is gradually decreased to 10 degrees or to the lowest tolerable temperature without shivering. | Drug: Fenoterol<br>* Intravenous infusion<br>* Other names: beta2 adrenoreceptor agonist;Other: Mild cold exposure<br>* Body surface cooling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BAT SUVmean | 18F-FDG uptake into the supra-clavicular brown adipose tissue as determined by 18F-FDG PET-CT after the respective study intervention | 30 minutes after end of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BAT SUVmax | maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0) | 30 minutes after intervention | 
| BAT Volume | volume of supraclavicular adipose tissue (according to BARCIST 1.0) | 30 minutes after intervention | 
| BAT glycolytic volume | volume of supraclavicular adipose tissue x SUVmean (according to BARCIST 1.0) | 30 minutes after intervention | 
| Change in energy expenditure | Quantitative change in EE above resting metabolic rate in response to the respective study intervention. Measured by indirect calorimetry. | First and last 30 minutes of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brown adipose tissue, beta2-adrenergic agonist, cold exposure