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Completed

NCT Number: NCT06035081

CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning

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

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Key information

Conditions

Healthy

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Department of Endocrinology and Internal Medicine

Aarhus, State, 8200, Denmark

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Prednisolone

Drug

see arm description

Placebo

Other

Placebo similar to prednisolone

Primary outcomes

  1. Change in Sleeping RER

    Time frame: Study day 1 and 2 (7 weeks apart)

    Change in respiratory exchange ratio (RER) during sleep between placebo and prednisolone

  2. Change in TEE

    Time frame: Study day 1 and 2 (7 weeks apart)

    Change in Total Energy Expenditure between placebo and prednisolone

  3. Change in REE

    Time frame: Study day 1 and 2 (7 weeks apart)

    Change in Resting Energy Expenditure between placebo and prednisolone and morning/evening

  4. Change in RER from fasting to feeding

    Time frame: 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 outcomes

  1. Change in PAEE

    Time frame: Study day 1 and 2 (7 weeks apart)

    Change in Physical Activity related Energy Expenditure (PAEE) between placebo and prednisolone and morning/evening

  2. Change in SEE

    Time frame: Study day 1 and 2 (7 weeks apart)

    Change in Sleeping Energy Expenditure (PAEE) between placebo and prednisolone

  3. Change in DIT

    Time frame: Study day 1 and 2 (7 weeks apart)

    Change in diet-induced thermogenesis between placebo and prednisolone and prednisolone and morning/evening

  4. Change in clock gene mRNA levels leukocytes

    Time frame: 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

  5. Change in clock gene mRNA levels adipose tissue

    Time frame: 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

  6. Change in clock gene mRNA levels skeletal muscle

    Time frame: 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

  7. Change in appetite

    Time frame: 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

  8. Change in ad libitum food intake

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by caloric intake between placebo and prednisolone and morning/evening

  9. Change in food intake at home

    Time frame: Intervention period 1 and 2 (7 weeks apart)

    Measured by dietary registration during prednisolone and placebo

  10. Change in fasting lipid oxidation rates

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening

  11. Change in lipid oxidation rates from fasting to fed

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening

  12. Change in glucose oxidation rates from fasting to fed

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening

  13. Change in fasting glucose oxidation rates

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening

  14. Change in fasting protein oxidation rates

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening

  15. Change in protein oxidation rates from fasting to fed

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening

  16. Change in ghrelin levels

    Time frame: 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

  17. Change in LEAP-2 levels

    Time frame: 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

  18. Change in GLP-1 levels

    Time frame: 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

  19. Change in GIP levels

    Time frame: 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

  20. Change in Glucose levels

    Time frame: 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

  21. Change in Insulin levels

    Time frame: 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

  22. Change in Glucagon levels

    Time frame: 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

  23. Change in Gastrin levels

    Time frame: 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

  24. Change in CCK levels

    Time frame: 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

  25. Change in cortisol levels

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured successively over 24 hours in serum during study days

  26. Change in FAP cells in skeletal muscle

    Time frame: 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

  27. Change in FAP cells in adipose tissue

    Time frame: 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

  28. Change in physical activity levels

    Time frame: Intervention period 1 and 2 (7 weeks apart)

    Measured by actigraph during study periods

  29. Change in IPAQ-7

    Time frame: Intervention period 1 and 2 (7 weeks apart)

    Measured by Internation Physical Activity Questionnaire

  30. Change in sleep quality (measured)

    Time frame: Intervention period 1 and 2 (7 weeks apart)

    Measured by actigraph during study periods

  31. Change in sleep quality (reported)

    Time frame: Intervention period 1 and 2 (7 weeks apart)

    Measured by Pittsburgh Sleep Quality Index questionnaire

  32. Change in sleep quality

    Time frame: Study day 1 and 2 (7 weeks apart)

    Measured by polysomnography

  33. Change in HADS

    Time frame: 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)

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

  • Aarhus University Hospital

Registry information

Acronym: CIRCLE

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Sep 13, 2023
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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