Brown Adipose Tissue
Conditions
Keywords
glucocorticoids, brown adipose tissue, cold induced thermogenesis
Brief summary
Interventional, Placebo controlled cross-over study to investigate the short-term effects of glucocorticoids (prednisone) on human brown adipose tissue.
Detailed description
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.
Interventions
DRUGPrednisone
2 tablets of Prednisone 20 Mg in the morning
DRUGPlacebo
2 Placebo tablets in the morning
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cold induced thermogenesis | at the end of each treatment period (day 7). Prednisone vs. Placebo | : Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus determined by indirect calorimetry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| volume of supraclavicular BAT | at the end of each treatment period (day 7). Prednisone vs. Placebo | determined by MRI |
| fat fraction of supraclavicular BAT | at the end of each treatment period (day 7). Prednisone vs. Placebo | determined by MRI |
| cold stimulated FGD uptake in brown adipose tissue | at the end of each treatment period (day 7). Prednisone vs. Placebo | determined as SUVmean by FDG-PET/CT |
| SUVmax in the supraclavicular adipose tissue depot | at the end of each treatment period (day 7). Prednisone vs. Placebo | determined by FDG-PET/CT |
Other
| Measure | Time frame |
|---|---|
| Expression levels of genes involved in thermogenesis and white to brown adipose tissue transdifferentiation in supraclavicular adipose tissue. | at the end of each treatment period (day 7). Prednisone vs. Placebo |
| FGF21 level before and after mild cold stimulus | at the end of each treatment period (day 7). Prednisone vs. Placebo |
| Glucose level before and after mild cold stimulus | at the end of each treatment period (day 7). Prednisone vs. Placebo |
Countries
Switzerland
Outcome results
None listed