Glucocorticoid Long-term Administration: Effect on Cold Induced Energy Expenditure and Resting Metabolic Rate

Study Overview
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Brief Summary
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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
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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.

Official Title
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Glucocorticoid Long-term Administration: Effect on Cold Induced Energy Expenditure and Resting Metabolic Rate

Conditions
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Thermoregulation Impairment

Intervention / Treatment
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* Diagnostic Test: Indirect calorimetry
* Diagnostic Test: Skin Temperature
* Diagnostic Test: Dual energy X-ray Absorptiometry (DXA)
* Diagnostic Test: Blood Sampling
* Diagnostic Test: FDG-PET
* Diagnostic Test: Capillary glucose
* Diagnostic Test: Biopsy of supraclavicular adipose tissue (optional)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients starting glucocorticoids<br>Patients starting a glucocorticoid therapy measuring primary and secondary endpoints before and after at least 4 weeks of treatment. | Diagnostic Test: Indirect calorimetry<br>* Resting energy expenditure<br>Diagnostic Test: Skin Temperature<br>* Temperature: supraclavicular, infraclavicular, abdominal, mid-thigh, non-dominant lower arm, middle finger tip, left lower leg, left dorsal foot, ear thermometer<br>Diagnostic Test: Dual energy X-ray Absorptiometry (DXA)<br>* Body composition<br>Diagnostic Test: Blood Sampling<br>* thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), HbA1c, Fibroblast growth factor 21 (FGF21)<br>Diagnostic Test: FDG-PET<br>* Dynamic PET scanning of the neck-region<br>Diagnostic Test: Capillary glucose<br>* Prior to fluorodeoxyglucose (FDG)-PET in order to avoid hyperglycemia<br>Diagnostic Test: Biopsy of supraclavicular adipose tissue (optional)<br>* Ultrasound guided biopsy of the supraclavicular adipose tissue<br>|
| Patients stopping glucocorticoids<br>Patients stopping a glucocorticoid therapy measuring primary and secondary endpoints before weaning off glucocorticoids and after a period of at least 3 months. | Diagnostic Test: Indirect calorimetry<br>* Resting energy expenditure<br>Diagnostic Test: Skin Temperature<br>* Temperature: supraclavicular, infraclavicular, abdominal, mid-thigh, non-dominant lower arm, middle finger tip, left lower leg, left dorsal foot, ear thermometer<br>Diagnostic Test: Dual energy X-ray Absorptiometry (DXA)<br>* Body composition<br>Diagnostic Test: Blood Sampling<br>* thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), HbA1c, Fibroblast growth factor 21 (FGF21)<br>Diagnostic Test: FDG-PET<br>* Dynamic PET scanning of the neck-region<br>Diagnostic Test: Capillary glucose<br>* Prior to fluorodeoxyglucose (FDG)-PET in order to avoid hyperglycemia<br>Diagnostic Test: Biopsy of supraclavicular adipose tissue (optional)<br>* Ultrasound guided biopsy of the supraclavicular adipose tissue<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cold-induced thermogenesis (CIT) under glucocorticoids | 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) | Change from glucocortoid start to +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting metabolic rate (RMR) | Comparison of RMR of patients starting GCs or patients stopping GCs, measured by indirect calorimetry | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | 
| Body composition | Comparison of body composition concerning muscle mass and fat mass, determined by DXA | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | 
| Cold stimulated glucose uptake into supraclavicular BAT | Determination of 'standardized uptake value' (SUV) mean in two volumes of interest on the supraclavicular adipose tissue, after PET-CT | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | 
| SUV max in supraclavicular adipose tissue depot | Determination of SUV max in the supraclavicular adipose tissue, after positron emission tomography (PET)-CT | Baseline and +4 to 8 weeks into treatment/ +3 months after weaning off GCs (resp.) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoids, Brown Adipose tissue, Cold Induced Thermogenesis, Resting Metabolic Rate