Clinical trial NCT05294965: Beta 2 Adrenergic Stimulation vs Cold Exposure to Activate Human Brown Adipose Tissue
Official title: Beta 2 Adrenergic Stimulation vs Cold Exposure to Activate Human Brown Adipose Tissue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Thermogenesis
Keywords: brown adipose tissue
beta2-adrenergic agonist
cold exposure
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2022-03-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Open-label, cross-over trial in healthy volunteers with random sequence of the two study interventions
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: BAT SUVmean
timeFrame: 30 minutes after end of intervention
Secondary outcomes:
measure: BAT SUVmax
timeFrame: 30 minutes after intervention
measure: BAT Volume
timeFrame: 30 minutes after intervention
measure: BAT glycolytic volume
timeFrame: 30 minutes after intervention
measure: Change in energy expenditure
timeFrame: First and last 30 minutes of intervention
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Dept. of Endocrinology
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias Betz, MD
role: PRINCIPAL_INVESTIGATOR
References: