Clinical trial NCT03269747: Short Term Effect of Glucocorticoids on Brown Adipose Tissue Thermogenesis in Humans
Official title: Short Term Effect of Glucocorticoids on Brown Adipose Tissue Thermogenesis in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Brown Adipose Tissue
Keywords: glucocorticoids
brown adipose tissue
cold induced thermogenesis
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2017-09-01
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cold induced thermogenesis
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
Secondary outcomes:
measure: fat fraction of supraclavicular BAT
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: volume of supraclavicular BAT
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: cold stimulated FGD uptake in brown adipose tissue
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: SUVmax in the supraclavicular adipose tissue depot
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
Other outcomes:
measure: Glucose level before and after mild cold stimulus
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: FGF21 level before and after mild cold stimulus
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: Expression levels of genes involved in thermogenesis and white to brown adipose tissue transdifferentiation in supraclavicular adipose tissue.
timeFrame: at the end of each treatment period (day 7). Prednisone vs. Placebo
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Endocrinology
state: BS
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias J Betz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fischer JGW, Maushart CI, Becker AS, Muller J, Madoerin P, Chirindel A, Wild D, Ter Voert EEGW, Bieri O, Burger I, Betz MJ. Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity. EJNMMI Res. 2020 Jul 22;10(1):85. doi: 10.1186/s13550-020-00665-7.