Short Term Effect of Glucocorticoids on Brown Adipose Tissue Thermogenesis in Humans

Study Overview
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Brief Summary
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Interventional, Placebo controlled cross-over study to investigate the short-term effects of glucocorticoids (prednisone) on human brown adipose tissue.

Detailed Description
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Active brown adipose tissue (BAT) has recently been unambiguously discovered in human adults. Active BAT increases energy expenditure and improves glucose tolerance. Pharmacological use of glucocorticoids (GCs) is widespread in clinical practice due to their high anti-inflammatory efficacy. While short-term administration even of high doses usually is well tolerated, long-term use of medium to high amounts of GCs leads to unfavorable metabolic changes, characterized by an increase in intra-abdominal fat mass, a decrease in muscle mass and insulin resistance. In line with these well-known side-effects of GCs, several in vitro studies and animal models demonstrate an inhibiting effect of GCs on BAT thermogenesis.

Official Title
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Short Term Effect of Glucocorticoids on Brown Adipose Tissue Thermogenesis in Humans

Conditions
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Brown Adipose Tissue

Intervention / Treatment
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* Drug: Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers BMI between 19-27 kg/m2 Exclusion Criteria: Cold induced thermogenesis of less than 5% basal metabolic rate (determined during screening visit) Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product, History of depressive disorder, anxiety disorder History of tuberculosis or latent infection Increased intraocular pressure History of peptic / gastrointestinal ulcer disease Concomitant medication: Non-steroidal anti-inflammatory drugs (NSAID), other glucocorticoids, diuretics, antihypertensives, fibrates or statins, metformin Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, diabetes mellitus), Hypersensitivity to cold (e.g. Raynaud Syndrome) Allergy to local anesthetic Known or suspected non-compliance, drug or alcohol abuse, Inability to follow the procedures of the study Participation in another study with investigational drug within the 30 days preceding and during the present study, Previous enrolment into the current study, Enrolment of the investigator, his/her family members, employees and other dependent persons, Hypothyroidism without sufficient substitution Claustrophobia MRI incompatible implants 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: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prednisone<br>Prednisone 40 mg daily for 7 days | Drug: Prednisone<br>* 2 tablets of Prednisone 20 Mg in the morning<br>|
| Placebo Comparator: Placebo<br>Placebo daily for 7 days | Drug: Placebo<br>* 2 Placebo tablets in the morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cold induced thermogenesis | : Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus determined by indirect calorimetry | at the end of each treatment period (day 7). Prednisone vs. Placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fat fraction of supraclavicular BAT | determined by MRI | at the end of each treatment period (day 7). Prednisone vs. Placebo | 
| volume of supraclavicular BAT | determined by MRI | at the end of each treatment period (day 7). Prednisone vs. Placebo | 
| cold stimulated FGD uptake in brown adipose tissue | determined as SUVmean by FDG-PET/CT | at the end of each treatment period (day 7). Prednisone vs. Placebo | 
| SUVmax in the supraclavicular adipose tissue depot | determined by FDG-PET/CT | at the end of each treatment period (day 7). Prednisone vs. Placebo | 

 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