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

Early Phase 1

Completed

• Conditions: Thermogenesis
• Interventions: Drug: Fenoterol; Other: Mild cold exposure

• Registration Number: NCT05294965
• Lead Sponsor: University Hospital, Basel, Switzerland

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.

Study Timeline

• Study First Submitted: 2022-02-09
• Study First Submitted QC: 2022-03-14
• Study First Posted: 2022-03-24
• Study Start: 2022-04-27
• Primary Completion: 2023-03-06
• Study Completion: 2023-03-06
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-25
• Last Update Posted: 2023-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• BMI 18,5-23 kg/m2 or 30-35 kg/m2

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Normal weight	Mild cold exposure	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. 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.
Overweight	Mild cold exposure	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. 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.
Normal weight	Fenoterol	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. 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.
Overweight	Fenoterol	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. 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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
BAT glycolytic volume	30 minutes after intervention	volume of supraclavicular adipose tissue x SUVmean (according to BARCIST 1.0)
BAT Volume	30 minutes after intervention	volume of supraclavicular adipose tissue (according to BARCIST 1.0)
BAT SUVmax	30 minutes after intervention	maximum SUV in supraclavicular adipose tissue (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.

Trial Locations

Locations (1)

University Hospital Basel, Dept. of Endocrinology; 🇨🇭 Basel, Switzerland