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

Thermoregulation Impairment Clinical Trial

— GLACIER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03949361
• Other study ID #: EKNZ 2017-01742
• Status: Completed
• Start date: June 1, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: January 2022
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Thermoregulation Impairment

Intervention

Diagnostic Test:
• Indirect calorimetry
Resting energy expenditure
• Skin Temperature
Temperature: supraclavicular, infraclavicular, abdominal, mid-thigh, non-dominant lower arm, middle finger tip, left lower leg, left dorsal foot, ear thermometer
• Dual energy X-ray Absorptiometry (DXA)
Body composition
• Blood Sampling
thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), HbA1c, Fibroblast growth factor 21 (FGF21)
• FDG-PET
Dynamic PET scanning of the neck-region
• Capillary glucose
Prior to fluorodeoxyglucose (FDG)-PET in order to avoid hyperglycemia
• Biopsy of supraclavicular adipose tissue (optional)
Ultrasound guided biopsy of the supraclavicular adipose tissue

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Department of Endocrinology	Basel	BS

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	ETH Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.)
Secondary	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.)
Secondary	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.)
Secondary	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.)