Healthy
Conditions
Keywords
glucocorticoids, circadian rhythm, metabolism
Brief summary
The aim of this project is to study the effects of exogenous glucocorticoid exposure on substrate metabolism, energy expenditure and correlates of circadian rhythmicity in healthy adults. The hypotheses are: Short-term high dose glucocorticoid exposure in healthy subjects disrupts: * The inherent circadian pattern of the respiratory exchange ratio and REE * Sleep quality, appetite and food intake * Clock gene expression and function in adipose tissue, skeletal muscle and blood leukocytes
Interventions
DRUGPrednisolone
see arm description
OTHERPlacebo
Placebo similar to prednisolone
Sponsors
Aarhus University Hospital
University of Aarhus
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 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male sex * BMI 20-30 kg/m2 * Written informed consent
Exclusion criteria
* Any chronic disease requiring daily medication excluding atopic skin or hay fever * Alcohol consumption \>21 units per week * Strong CYP3A4 inhibitors or inducers * Use of glucocorticoid (GC) formulations: Inhaled corticosteroids, intra-articular or intramuscular injections, steroid creams European steroid group IV-V used in the genital area * Permitted glucocorticoid formulations: eye-drops, nasal spray, GC creams European steroid group I-III, and European steroid group IV-V used in the non-genital area only * Shift work * Severe claustrophobia * Use of melatonin * Previous diagnosis of a sleep disorder * Known severe sleep apnea (\>30 respiration breaks/hour over 10 seconds) * Deemed unable to complete the study safely by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sleeping RER | Study day 1 and 2 (7 weeks apart) | Change in respiratory exchange ratio (RER) during sleep between placebo and prednisolone |
| Change in TEE | Study day 1 and 2 (7 weeks apart) | Change in Total Energy Expenditure between placebo and prednisolone |
| Change in REE | Study day 1 and 2 (7 weeks apart) | Change in Resting Energy Expenditure between placebo and prednisolone and morning/evening |
| Change in RER from fasting to feeding | Study day 1 and 2 (7 weeks apart) | Change in respiratory exchange ratio (RER) after standard meal between placebo and prednisolone and morning/evening |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in clock gene mRNA levels adipose tissue | Study day 1 and 2 (7 weeks apart) | Change in mRNA expression levels in adipose tissue biopsies between placebo and prednisolone and prednisolone and morning/evening |
| Change in clock gene mRNA levels skeletal muscle | Study day 1 and 2 (7 weeks apart) | Change in mRNA expression levels in skeletal muscle tissue biopsies between placebo and prednisolone and prednisolone and morning/evening |
| Change in appetite | Study day 1 and 2 (7 weeks apart) | Measured by numerical rating scale on parameters hunger, fullness, satiety, desire and prospective consumption with values 1 (not at all) to 10 (maximally present) before and after ad libitum meal and standard meal, and between placebo and prednisolone and morning/evening. The scale is adapted from PMID: 20122136 |
| Change in ad libitum food intake | Study day 1 and 2 (7 weeks apart) | Measured by caloric intake between placebo and prednisolone and morning/evening |
| Change in food intake at home | Intervention period 1 and 2 (7 weeks apart) | Measured by dietary registration during prednisolone and placebo |
| Change in fasting lipid oxidation rates | Study day 1 and 2 (7 weeks apart) | Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening |
| Change in lipid oxidation rates from fasting to fed | Study day 1 and 2 (7 weeks apart) | Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening |
| Change in glucose oxidation rates from fasting to fed | Study day 1 and 2 (7 weeks apart) | Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening |
| Change in fasting glucose oxidation rates | Study day 1 and 2 (7 weeks apart) | Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening |
| Change in fasting protein oxidation rates | Study day 1 and 2 (7 weeks apart) | Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening |
| Change in protein oxidation rates from fasting to fed | Study day 1 and 2 (7 weeks apart) | Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening |
| Change in ghrelin levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in LEAP-2 levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in GLP-1 levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in PAEE | Study day 1 and 2 (7 weeks apart) | Change in Physical Activity related Energy Expenditure (PAEE) between placebo and prednisolone and morning/evening |
| Change in Glucose levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in Insulin levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in Glucagon levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in Gastrin levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in CCK levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in cortisol levels | Study day 1 and 2 (7 weeks apart) | Measured successively over 24 hours in serum during study days |
| Change in FAP cells in skeletal muscle | Study day 1 and 2 (7 weeks apart) | Fibro-adipogenic progenitor cells levels and characteristics in skeletal muscle tissue biopsies between placebo and prednisolone and prednisolone and morning/evening |
| Change in FAP cells in adipose tissue | Study day 1 and 2 (7 weeks apart) | Fibro-adipogenic progenitor cells levels and characteristics in adipose tissue biopsies between placebo and prednisolone and prednisolone and morning/evening |
| Change in physical activity levels | Intervention period 1 and 2 (7 weeks apart) | Measured by actigraph during study periods |
| Change in IPAQ-7 | Intervention period 1 and 2 (7 weeks apart) | Measured by Internation Physical Activity Questionnaire |
| Change in sleep quality (measured) | Intervention period 1 and 2 (7 weeks apart) | Measured by actigraph during study periods |
| Change in sleep quality (reported) | Intervention period 1 and 2 (7 weeks apart) | Measured by Pittsburgh Sleep Quality Index questionnaire |
| Change in sleep quality | Study day 1 and 2 (7 weeks apart) | Measured by polysomnography |
| Change in HADS | Intervention period 1 and 2 (7 weeks apart) | Measured by Hospital Anxiety and Depression Scale (HADS), a 14-question instrument with 7 questions measuring anxiety and 7 measuring depression. Each is scored between 0 (no impairment) and 3 (severe impairment) |
| Change in GIP levels | Study day 1 and 2 (7 weeks apart) | Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening |
| Change in SEE | Study day 1 and 2 (7 weeks apart) | Change in Sleeping Energy Expenditure (PAEE) between placebo and prednisolone |
| Change in DIT | Study day 1 and 2 (7 weeks apart) | Change in diet-induced thermogenesis between placebo and prednisolone and prednisolone and morning/evening |
| Change in clock gene mRNA levels leukocytes | Study day 1 and 2 (7 weeks apart) | Change in mRNA expression levels in blood leukocytes between placebo and prednisolone and prednisolone and morning/evening |
Countries
Denmark
Outcome results
None listed