Intermittent Cold Exposure and Brown Adipose Tissue Hyperplasia

NCT07048405 | Recruiting

• 2 other identifiers: 35011724/SS/0094
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (4)

• Changes in brown adipose tissue activity/mass before and after cold acclimation protocol

  year after

• Energy expenditure

  year after

• Skin and core temperature

  year after

• Immune cell levels

  year after

Study Arms (1)

Healthy normal weight subjects

EXPERIMENTAL

Other: Cooling; Procedure: Biopsies; Radiation: Injection of 18F-FDG; Other: Indirect calorimetry; Other: Electromyogram; Other: Core and skin temperature monitoring

Interventions

Cooling OTHER

Participants 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.

Healthy normal weight subjects

Biopsies PROCEDURE

Under 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.

Also known as: brown adipose tissue biopsy, white adipose tissue biopsy, skeletal muscle biopsy

Healthy normal weight subjects

Injection of 18F-FDG RADIATION

Intravenous 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.

Healthy normal weight subjects

Indirect calorimetry OTHER

Participants 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.

Healthy normal weight subjects

Electromyogram OTHER

Skin 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.

Healthy normal weight subjects

Core and skin temperature monitoring OTHER

Participants 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.

Healthy normal weight subjects

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Contra-indication to PET/CT scan
• Allergy to local anaesthetic

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

RECRUITING

MeSH Terms

Interventions

Cool-Down Exercise; Biopsy; Calorimetry, Indirect

Intervention Hierarchy (Ancestors)

Post-Exercise Recovery Techniques; Physical Therapy Modalities; Therapeutics; Rehabilitation; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Calorimetry; Chemistry Techniques, Analytical

Central Study Contacts

María Paula Huertas Caycedo

CONTACT

01312429196; m.p.huertas-caycedo@sms.ed.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: July 2, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)