Thermoregulation Impairment
Conditions
Keywords
Glucocorticoids, Brown Adipose tissue, Cold Induced Thermogenesis, Resting Metabolic Rate
Brief summary
The aim of the study is to investigate whether treatment with glucocorticoids leads to a change in heat production of the human body at mild cold conditions.
Detailed description
Brown adipose tissue (BAT) is a thermogenic tissue that can convert chemical energy directly into heat due to the expression of uncoupling protein 1 (UCP1) protein. Data from preclinical studies shows that glucocorticoids (GCs) inhibit the function of BAT. In clinical practice GCs are often administered due tue their antiinflammatory properties making the investigation of short term (e.g. one week) and long therm (several months) effects practically relevant. This study's objective is to evaluate the effect of glucocorticoid treatment on cold induced thermogenesis (CIT) in humans.
Interventions
DIAGNOSTIC_TESTIndirect calorimetry
Resting energy expenditure
DIAGNOSTIC_TESTSkin Temperature
Temperature: supraclavicular, infraclavicular, abdominal, mid-thigh, non-dominant lower arm, middle finger tip, left lower leg, left dorsal foot, ear thermometer
DIAGNOSTIC_TESTDual energy X-ray Absorptiometry (DXA)
Body composition
DIAGNOSTIC_TESTBlood Sampling
thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), HbA1c, Fibroblast growth factor 21 (FGF21)
DIAGNOSTIC_TESTFDG-PET
Dynamic PET scanning of the neck-region
DIAGNOSTIC_TESTCapillary glucose
Prior to fluorodeoxyglucose (FDG)-PET in order to avoid hyperglycemia
DIAGNOSTIC_TESTBiopsy of supraclavicular adipose tissue (optional)
Ultrasound guided biopsy of the supraclavicular adipose tissue
Sponsors
ETH Zurich
University Hospital, Basel, Switzerland
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Planned therapy with at least 7.5 mg prednisone equivalent per day or higher for more than 28 days (group A) * Planned weaning off glucocorticoid therapy which lasted al least 28 days with a dosage of at least 7.5 mg prednisone (group B) * BMI 19-30 kg/m2 * Informed Consent as documented by signature
Exclusion criteria
* Insufficient thyroid hormone substitution in case of hypothyroidism * Uncontrolled diabetes mellitus (HbA1c \>7.5%) * Severe concomitant diseases: chronic heart failure, liver cirrhosis, kidney failure, active cancer * Known hypersensitivity to cold, e.g. primary or secondary Raynaud's Syndrome * Known or suspected non-compliance * Abuse of alcohol or illicit drugs * Claustrophobia * Women who are pregnant or breast feeding * Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc of the participant * Previous enrolment into the current study * Enrolment into another study using ionizing radiation within the previous 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cold-induced thermogenesis (CIT) under glucocorticoids | Change from glucocortoid start to +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | Comparison of CIT change off-glucocorticoids with warm ischemia time (WIT) on-glucocorticoids by using indirect calorimetry. Comparing two Groups (Observation group A and B) we will address the CIT change from glucocorticoid start to 4-8 weeks into treatment (group A) and the CIT change from glucocorticoid therapy to weaning off upon more than 3 months after glucocorticoid withdrawal (group B) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting metabolic rate (RMR) | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | Comparison of RMR of patients starting GCs or patients stopping GCs, measured by indirect calorimetry |
| Body composition | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | Comparison of body composition concerning muscle mass and fat mass, determined by DXA |
| Cold stimulated glucose uptake into supraclavicular BAT | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | Determination of 'standardized uptake value' (SUV) mean in two volumes of interest on the supraclavicular adipose tissue, after PET-CT |
| SUV max in supraclavicular adipose tissue depot | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | Determination of SUV max in the supraclavicular adipose tissue, after positron emission tomography (PET)-CT |
Countries
Switzerland
Outcome results
None listed