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

NCT ID: NCT05294965

Last Updated: 2023-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-27
• Study Completion Date: 2023-03-06

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.

Conditions

Thermogenesis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Normal weight

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.

Group Type: EXPERIMENTAL

Fenoterol

Intervention Type: DRUG

Intravenous infusion

Mild cold exposure

Intervention Type: OTHER

Body surface cooling

Overweight

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.

Group Type: EXPERIMENTAL

Fenoterol

Intervention Type: DRUG

Intravenous infusion

Mild cold exposure

Intervention Type: OTHER

Body surface cooling

Interventions

Fenoterol

Intravenous infusion

Intervention Type: DRUG

Mild cold exposure

Body surface cooling

Intervention Type: OTHER

Other Intervention Names

beta2 adrenoreceptor agonist

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthias Betz, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel, Dept. of Endocrinology

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

EKNZ 2022-00037

Identifier Type: -

Identifier Source: org_study_id