Intermittent Cold Exposure and Brown Adipose Tissue Hyperplasia

Not Applicable

Recruiting

• Conditions: 18F-FDG PET/CT; Cold Exposure; Brown Adipose Tissue

• Registration Number: NCT07048405
• Lead Sponsor: University of Edinburgh

Brief Summary

This clinical trial explores how repeated short-term cold exposure impacts the molecular and physiological function of brown adipose tissue (BAT), a thermogenic organ associated with improved cardiometabolic health. While intermittent cold exposure has been shown to increase BAT activity and mass, as measured by fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans, the molecular adaptations within BAT and other thermogenic tissues including skeletal muscle and white adipose tissue (WAT) remain poorly understood.

Healthy adults aged 18 to 40 years (6 males and 6 females) will participate in a 10-day cold acclimation protocol (2 hours per day using water-perfused cooling blankets). The primary objective is to determine how cold exposure alters cellular heterogeneity and gene expression in BAT, WAT, and skeletal muscle.

Participants will undergo baseline assessments, including measurements of energy expenditure, core and skin temperature, muscle activity, and blood sampling, each performed in both warm and cold conditions. These assessments will be followed by dynamic total-body PET/CT imaging during cold exposure and tissue biopsies from BAT, subcutaneous WAT, and skeletal muscle. These procedures will be repeated after the cold acclimation protocol to evaluate physiological and molecular changes. Additional outcomes include changes in energy expenditure, cold tolerance, and immune cell responses induced by cold exposure.

Detailed Description

Twelve healthy adults aged 18-40 years old (6 female, 6 male) will:

* Attend baseline visits in both warm and cold conditions for blood sampling, measurement of energy expenditure, skin and core temperature, muscle activity. This will be followed by dynamic total-body 18F-FDG PET/CT scan during cold exposure.

* Undergo biopsies of BAT (supraclavicular), skeletal muscle (vastus lateralis), and subcutaneous WAT (periumbilical) under local anesthesia.

* Complete 10 consecutive days of cold acclimation (2 hours per day) using water-perfused cooling blankets.

* Return for follow-up assessments, including repeat blood sampling, energy expenditure, temperature measurements, PET/CT imaging, and tissue biopsies to evaluate post-acclimation changes.

Study Timeline

• Status Verified: 2025-05
• Study Start: 2025-05-01
• Study First Submitted: 2025-05-06
• Study First Submitted QC: 2025-06-30
• Study First Posted: 2025-07-02
• Last Update Submitted: 2025-07-03
• Last Update Posted: 2025-07-09
• Primary Completion: 2026-07
• Study Completion: 2026-07-01

Recruitment & Eligibility

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

Inclusion Criteria

• Aged 18-40 years
• Body mass index 18.5-25 kg/m2
• Weight change of less than 5% in the past 6 months
• No acute or chronic medical conditions
• On no regular medications (other than contraceptives in female participants)
• No claustrophobia
• Alcohol intake ≤14 units/ week
• Screening blood tests within acceptable limits (of no clinical significance)
• Not currently pregnant, lactating or breastfeeding (female participants only)
• Ability to provide informed consent.

Exclusion Criteria

• Not meeting inclusion criteria
• Contra-indication to PET/CT scan
• Allergy to local anaesthetic

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Tissue transcriptional changes derived from cold exposure	1 year	We will be analysing and comparing gene expression from nuclei extracted from BAT, WAT and skeletal muscle before and after cold the 10-day cold acclimation protocol.

Secondary Outcome Measures

Name	Time	Method
Changes in brown adipose tissue activity/mass before and after cold acclimation protocol	year after	BAT activity/mass will be measured using the glucose analogue 18-FDG radiotracer combine with PET/CT.
Energy expenditure	year after	Energy expenditure measured with indirect calorimetry before and after cold acclimation protocol to evaluated any changes in response to intermittent cold exposure.
Skin and core temperature	year after	Measurement of skin and core temperature before and after the cold acclimation protocol
Immune cell levels	year after	Analyse the percentage of immune cell populations before and after cold acclimation

Trial Locations

Locations (1)

Royal Infirmary of Edinburgh; 🇬🇧 Edinburgh, United Kingdom