CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning
- Registration Number
- NCT06035081
- Lead Sponsor
- University of Aarhus
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 10
- Male sex
- BMI 20-30 kg/m2
- Written informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Prednisolone first, then placebo Prednisolone Prednisolone 12.5 mg twice daily for 5 days. Placebo twice daily for 5 days Prednisolone first, then placebo Placebo Prednisolone 12.5 mg twice daily for 5 days. Placebo twice daily for 5 days Placebo first, then prednisolone Prednisolone Placebo twice daily for 5 days Prednisolone 12.5 mg twice daily for 5 days. Placebo first, then prednisolone Placebo Placebo twice daily for 5 days Prednisolone 12.5 mg twice daily for 5 days.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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 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 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 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 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 SEE Study day 1 and 2 (7 weeks apart) Change in Sleeping Energy Expenditure (PAEE) between placebo and prednisolone
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 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 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 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 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 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 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 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 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 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 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 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
Trial Locations
- Locations (1)
Department of Endocrinology and Internal Medicine
🇩🇰Aarhus, State, Denmark