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

Healthy Clinical Trial

— CIRCLE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06035081
• Other study ID #: 1-10-72-83-22
• Status: Recruiting
• Phase: N/A
• Start date: September 15, 2023
• Est. completion date: March 2024

Study information

• Verified date: September 2023
• Source: University of Aarhus
• Contact: Simon B Hansen, MD
• Phone: 41111574
• Email: simhan[@]clin.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Prednisolone
see arm description

Other:
• Placebo
Placebo similar to prednisolone

Locations

Country	Name	City	State
Denmark	Department of Endocrinology and Internal Medicine	Aarhus	State

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Sleeping RER	Change in respiratory exchange ratio (RER) during sleep between placebo and prednisolone	Study day 1 and 2 (7 weeks apart)
Primary	Change in TEE	Change in Total Energy Expenditure between placebo and prednisolone	Study day 1 and 2 (7 weeks apart)
Primary	Change in REE	Change in Resting Energy Expenditure between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Primary	Change in RER from fasting to feeding	Change in respiratory exchange ratio (RER) after standard meal between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in PAEE	Change in Physical Activity related Energy Expenditure (PAEE) between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in SEE	Change in Sleeping Energy Expenditure (PAEE) between placebo and prednisolone	Study day 1 and 2 (7 weeks apart)
Secondary	Change in DIT	Change in diet-induced thermogenesis between placebo and prednisolone and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in clock gene mRNA levels leukocytes	Change in mRNA expression levels in blood leukocytes between placebo and prednisolone and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in clock gene mRNA levels adipose tissue	Change in mRNA expression levels in adipose tissue biopsies between placebo and prednisolone and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in clock gene mRNA levels skeletal muscle	Change in mRNA expression levels in skeletal muscle tissue biopsies between placebo and prednisolone and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in appetite	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	Study day 1 and 2 (7 weeks apart)
Secondary	Change in ad libitum food intake	Measured by caloric intake between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in food intake at home	Measured by dietary registration during prednisolone and placebo	Intervention period 1 and 2 (7 weeks apart)
Secondary	Change in fasting lipid oxidation rates	Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in lipid oxidation rates from fasting to fed	Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in glucose oxidation rates from fasting to fed	Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in fasting glucose oxidation rates	Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in fasting protein oxidation rates	Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in protein oxidation rates from fasting to fed	Measured by whole room Indirect calorimetry between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in ghrelin levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in LEAP-2 levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in GLP-1 levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in GIP levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in Glucose levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in Insulin levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in Glucagon levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in Gastrin levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in CCK levels	Measured in serum before and after ad libitum meals and standard meals; between placebo and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in cortisol levels	Measured successively over 24 hours in serum during study days	Study day 1 and 2 (7 weeks apart)
Secondary	Change in FAP cells in skeletal muscle	Fibro-adipogenic progenitor cells levels and characteristics in skeletal muscle tissue biopsies between placebo and prednisolone and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in FAP cells in adipose tissue	Fibro-adipogenic progenitor cells levels and characteristics in adipose tissue biopsies between placebo and prednisolone and prednisolone and morning/evening	Study day 1 and 2 (7 weeks apart)
Secondary	Change in physical activity levels	Measured by actigraph during study periods	Intervention period 1 and 2 (7 weeks apart)
Secondary	Change in IPAQ-7	Measured by Internation Physical Activity Questionnaire	Intervention period 1 and 2 (7 weeks apart)
Secondary	Change in sleep quality (measured)	Measured by actigraph during study periods	Intervention period 1 and 2 (7 weeks apart)
Secondary	Change in sleep quality (reported)	Measured by Pittsburgh Sleep Quality Index questionnaire	Intervention period 1 and 2 (7 weeks apart)
Secondary	Change in sleep quality	Measured by polysomnography	Study day 1 and 2 (7 weeks apart)
Secondary	Change in HADS	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)	Intervention period 1 and 2 (7 weeks apart)