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

• Sponsor: University of Aarhus (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT06035081
• Collaborator: Aarhus University Hospital (Other)
• Enrollment: 10
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 5.5
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Prednisolone	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning
• Anticipated Study Start Date: Sep 15, 2023
• Anticipated Primary Completion Date: Mar 1, 2024
• Anticipated Study Completion Date: Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prednisolone first, then placebo Prednisolone 12.5 mg twice daily for 5 days. Placebo twice daily for 5 days	Drug: Prednisolone; see arm description
Experimental: Placebo first, then prednisolone Placebo twice daily for 5 days Prednisolone 12.5 mg twice daily for 5 days.	Drug: Prednisolone; see arm description

Outcome Measures

Primary Outcome Measures

1. Change in Sleeping RER [Study day 1 and 2 (7 weeks apart)]

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

2. Change in TEE [Study day 1 and 2 (7 weeks apart)]

   Change in Total Energy Expenditure between placebo and prednisolone

3. Change in REE [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 [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

1. 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

2. Change in SEE [Study day 1 and 2 (7 weeks apart)]

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

3. 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

4. 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

5. 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

6. 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

7. Change in appetite [Study day 1 and 2 (7 weeks apart)]

   Measured by 10 point numerical rating scale before and after ad libitum meal and standard meal, and between placebo and prednisolone and morning/evening

8. 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

9. Change in food intake at home [Intervention period 1 and 2 (7 weeks apart)]

   Measured by dietary registration during prednisolone and placebo

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. Change in cortisol levels [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 [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 [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 [Intervention period 1 and 2 (7 weeks apart)]

    Measured by actigraph during study periods

29. Change in IPAQ-7 [Intervention period 1 and 2 (7 weeks apart)]

    Measured by Internation Physical Activity Questionnaire

30. Change in sleep quality (measured) [Intervention period 1 and 2 (7 weeks apart)]

    Measured by actigraph during study periods

31. Change in sleep quality (reported) [Intervention period 1 and 2 (7 weeks apart)]

    Measured by Pittsburgh Sleep Quality Index questionnaire

32. Change in sleep quality [Study day 1 and 2 (7 weeks apart)]

    Measured by polysomnography

33. Change in HADS [Intervention period 1 and 2 (7 weeks apart)]

    Measured by Hospital Anxiety and Depression Scale

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Endocrinology and Internal Medicine	Aarhus	State	Denmark	8200

Sponsors and Collaborators

• University of Aarhus
• Aarhus University Hospital

Investigators

• Study Director: Jens Otto L Jørgensen, Professor, Aarhus University Hospital
• Principal Investigator: Simon B Hansen, MD, Aarhus University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT06035081
• Other Study ID Numbers: 1-10-72-83-22
• First Posted: Sep 13, 2023
• Last Update Posted: Sep 13, 2023
• Last Verified: Sep 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Aarhus: glucocorticoids; circadian rhythm; metabolism
• Additional relevant MeSH terms: Prednisolone

Study Results

No Results Posted as of Sep 13, 2023