Effect of Caffeine on Cold-stimulated Brown Adipose Tissue Activity (ACROBAT)

The purpose of the study is to asses brown adipose tissue activity after a cold mild stimulus, preceded by 200mg caffeine or placebo administration.

Study Overview

• Status: Recruiting
• Conditions: Cold Exposure; Brown Adipose Tissue (BAT) Physiology
• Intervention / Treatment: Drug: Caffeine (200 mg); Drug: Placebo

Detailed Description

Brown adipose tissue (BAT) activation is typically through beta3-adrenoceptors (beta3-AR), but beta3-alone are less efficacious than cold in activating human BAT. Recent research suggests that adenosine, released during cold exposure, plays a key role in BAT thermogenesis. This study aims to investigate the role of the adenosine A2A receptor (A2AR) in BAT activation through a randomized trial with mild cold exposure and caffeine, a potent A2AR antagonist, to explore new therapeutic strategies for metabolic diseases.

This is a randomized, double-blind, placebo-controlled cross-over trial involving healthy volunteers. The study includes a screening visit and two main study visits (A and B), which will occur in random order.

During the two study visits, resting energy expenditure will be assessed by indirect calorimetry under warm conditions and following mild cold exposure, after administration of either caffeine or placebo. For cold exposure, participants will wear cooling sleeves around the waist, which gradually lower the surface body temperature to 10°C or to the lowest tolerable temperature without inducing shivering.

Additionally, BAT activity will be assessed using 18F-FDG PET/CT, performed 30 minutes after the injection of 75 MBq of 18F-FDG.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthias Betz, Prof.; Phone Number: 0041 61 556 56 54; Email: Matthias.Betz@usb.ch
• Study Contact Backup: Name: Jaël Senn, MD; Phone Number: 0041 61 328 70 79; Email: jaelrut.senn@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel, Department of Endocrinology
    • Contact: Matthias Betz, Prof.; Phone Number: 0041 61 556 56 54; Email: Matthias.Betz@usb.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI 18.5 to 25 kg/m2
• Able to give informed consent as documented by signature
• Moderate caffeine consumption (1 to 3 cups of coffee per day)
• Increase of EE in response to mild cold of ≥ 5% of REE

Exclusion Criteria:

• Known hypersensitivity or allergy to caffeine
• Concomitant medication other than prescription free analgesics (paracetamol and NSAID) and oral contraceptives
• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, cardiac arrhythmia, hypertension, diabetes mellitus, hyper- or hypothyroidism)
• History of depressive disorder or anxiety disorder
• Smoker / habitual tobacco use
• Habitual excessive alcohol use
• Regular consumption of caffeine containing energy drinks
• Weight change of >5% within 3 months prior to inclusion
• Systolic blood pressure >140 mmHg and/or diastolic blood pressure > 95 mmHg.
• Resting heart rate >90 bpm
• Hypersensitivity to cold (e.g. Raynaud syndrome)
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
• Enrolment of the investigator, his/her family members, employees, and other dependent persons
• Enrolment into another study using ionizing radiation within the previous 12 months.
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Caffeine; Participants will be administered a single dose of 200mg caffeine orally in study visite A, before exposing to a mild cold stimulus. Resting energy expenditure will be measured before an after administration of caffeine and cold exposure.	Drug: Caffeine (200 mg); single dose of 200mg caffeine orally in study visit A
Placebo Comparator: Placebo; Participants will be administered a single dose of placebo tablet orally in study visite B, before exposing to a mild cold stimulus. Resting energy expenditure will be measured before an after administration of placebo and cold exposure.	Drug: Placebo; single dose of 1 tablet Placebo in study visit B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BAT SUVmean	Description: 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 in study visit A and B.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BAT SUVmax	maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0) as determined by 18F-FDG PET-CT after the respective study intervention	30 minutes after intervention in study visit A and B.
BAT Volume	volume of supraclavicular adipose tissue (according to BARCIST 1.0) as determined by 18F-FDG PET-CT after the respective study intervention.	30 minutes after intervention in study visit A and B.
Cold induced thermogenesis (CIT)	rise in energy expenditure above baseline occurring during mild cold exposure in the respective study intervention.	immediately after the intervention (caffeine or placebo)
Resting energy expenditure (REE)	REE during warm conditions and at the end of cold exposure.	immediately after the intervention (caffeine or placebo)
Respiratory exchange ratio (RER):	Ratio between carbon dioxide production and oxygen consumption (VCO2/VO2) during the enregy expenditure (EE) measurements.	immediately after the intervention (caffeine or placebo)
Skin temperature	Changes in skin temperature after mild cold stimulus. It will be measured during the hole study visits during warm condition and after cold stimulation, using wireless temperature sensors (iButton Thermochron) attached to the skin at 11 pre-defined locations	immediately after the intervention (caffeine or placebo)
Metabolom and Lipidome profile	Plasma metabolome and lipidome profiles.	immediately after the intervention (caffeine or placebo)
Caffeine and its metabolites	Plasma caffeine and its metabolites.	immediately after the intervention (caffeine or placebo)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias Betz, Prof., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2026
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 2, 2025
• First Submitted That Met QC Criteria: May 15, 2025
• First Posted (Actual): May 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Xanthines; Caffeine
• Other Study ID Numbers: ACROBAT_V1_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No