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

Thermogenesis Clinical Trial

— ASCENT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05294965
• Other study ID #: EKNZ 2022-00037
• Status: Completed
• Phase: Early Phase 1
• Start date: April 27, 2022
• Est. completion date: March 6, 2023

Study information

• Verified date: September 2023
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 6, 2023
• Est. primary completion date: March 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Thermogenesis

Intervention

Drug:
• Fenoterol
Intravenous infusion

Other:
• Mild cold exposure
Body surface cooling

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Dept. of Endocrinology	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	BAT SUVmax	maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0)	30 minutes after intervention
Secondary	BAT Volume	volume of supraclavicular adipose tissue (according to BARCIST 1.0)	30 minutes after intervention
Secondary	BAT glycolytic volume	volume of supraclavicular adipose tissue x SUVmean (according to BARCIST 1.0)	30 minutes after intervention
Secondary	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