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

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

Study Overview

• Status: Completed
• Conditions: Brown Adipose Tissue
• Intervention / Treatment: Drug: Prednisone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4031
      • University Hospital Basel, Department of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prednisone; Prednisone 40 mg daily for 7 days	Drug: Prednisone; 2 tablets of Prednisone 20 Mg in the morning
Placebo Comparator: Placebo; Placebo daily for 7 days	Drug: Placebo; 2 Placebo tablets in the morning

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Glucose level before and after mild cold stimulus	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
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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2017
• Primary Completion (Actual): April 16, 2019
• Study Completion (Actual): April 16, 2019

Study Registration Dates

• First Submitted: August 30, 2017
• First Submitted That Met QC Criteria: August 30, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Actual): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: glucocorticoids; brown adipose tissue; cold induced thermogenesis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: EKNZ 2016-01859

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No