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

• ClinicalTrials.gov Identifier: NCT03949361
• Recruitment Status: Completed
• First Posted: May 14, 2019
• Last Update Posted: January 25, 2022
• Sponsor: University Hospital, Basel, Switzerland
• Collaborator: ETH Zurich
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

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.

Condition or disease	Intervention/treatment
Thermoregulation Impairment	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)

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 7 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Glucocorticoid Long-term Administration: Effect on Cold Induced Energy Expenditure and Resting Metabolic Rate
• Actual Study Start Date: June 1, 2019
• Actual Primary Completion Date: December 1, 2021
• Actual Study Completion Date: December 1, 2021

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Cold-induced thermogenesis (CIT) under glucocorticoids [ Time Frame: 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 Outcome Measures :

1. Resting metabolic rate (RMR) [ Time Frame: 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
2. Body composition [ Time Frame: 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
3. Cold stimulated glucose uptake into supraclavicular BAT [ Time Frame: 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
4. SUV max in supraclavicular adipose tissue depot [ Time Frame: 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

Biospecimen Retention:   Samples With DNA

Serum and plasma Optional biopsy of supraclavicular BAT

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients will be recruited via the outpatient clinics (endocrinology, rheumathology, ophthalmology, gastroenterology etc.) of the Basel University Hospital.

Criteria

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

Contacts and Locations

Locations

Switzerland

University Hospital Basel, Department of Endocrinology

Basel, BS, Switzerland, 4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

ETH Zurich

Investigators

• Study Director: Matthias Matthias, PD Dr. med; Klinik Endokrinologie, Diabetes und Metabolismus

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT03949361
• Other Study ID Numbers: EKNZ 2017-01742
• First Posted: May 14, 2019
• Last Update Posted: January 25, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Basel, Switzerland:

Glucocorticoids; Brown Adipose tissue; Cold Induced Thermogenesis; Resting Metabolic Rate