About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
Not meeting inclusion criteria
Contra-indication to PET/CT scan
Allergy to local anaesthetic
Trial design
Single group
Treatments tested in this trial
Cooling
Other interventionParticipants will undergo cold exposure during the baseline and final visits (2.5 hours each visit), as well as throughout the 10-day cold acclimation period (2 hours per day). This will be achieved using water-perfused blankets set to individualized temperatures, selected to elicit comparable physiological responses across participants.
Biopsies
Procedure/SurgeryUnder local anesthesia, biopsies will be obtained from the following sites: * Brown adipose tissue from the supraclavicular (collarbone) region, guided by computed tomography (CT). * White adipose tissue from the abdominal (periumbilical) area. * Skeletal muscle from the outer thigh, specifically the vastus lateralis. These biopsies will be performed both before and after the 10-day cold acclimation protocol.
Injection of 18F-FDG
RadiationIntravenous injection of 18F-FDG will be performed after 2 hours of cold exposure. This will be followed by a 30min dynamic total PET/CT scan while cold exposed using water-perfused blankets. These procedures will take place before and after the 10 day-cold acclimation protocol.
Indirect calorimetry
Other interventionParticipants will rest quietly while oxygen consumption and carbon dioxide production are continuously recorded using a indirect calorimeter. These data will be used to calculate energy expenditure and respiratory exchange ratio. This procedure will take place before and after the 10 day-cold acclimation protocol.
Electromyogram
Other interventionSkin surface electrodes will be placed on major skeletal muscles to measure shivering and muscle activity during both warm and cold conditions. This procedure will take place before and after the 10 day-cold acclimation protocol.
Core and skin temperature monitoring
Other interventionParticipants will ingest an electronic capsule that wirelessly and continuously monitors core body temperature. This procedure will be conducted before and after the 10-day cold acclimation protocol. Additionally, wireless temperature sensors will placed at multiple standardized sites on the body to measure skin temperature. This procedure will be performed before, during, and after the 10-day cold acclimation protocol.
Treatment groups
Trial outcomes
Primary outcomes
Tissue transcriptional changes derived from cold exposure
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 outcomes
Changes in brown adipose tissue activity/mass before and after cold acclimation protocol
BAT activity/mass will be measured using the glucose analogue 18-FDG radiotracer combine with PET/CT.
Energy expenditure
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
Measurement of skin and core temperature before and after the cold acclimation protocol
Immune cell levels
Analyse the percentage of immune cell populations before and after cold acclimation
Sponsors and contacts
Click on the lead sponsor to view all of their trials.