Clinical trial NCT06035081: CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning
Official title: CIRcadian Rhythms and CortisoL. Effects on Substrate Metabolism and Clock Gene Expression and Functioning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: glucocorticoids
circadian rhythm
metabolism
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2023-09-13
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Change in Sleeping RER
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in TEE
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in REE
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in RER from fasting to feeding
timeFrame: Study day 1 and 2 (7 weeks apart)
Secondary outcomes:
measure: Change in PAEE
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in SEE
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in DIT
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in clock gene mRNA levels leukocytes
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in clock gene mRNA levels adipose tissue
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in clock gene mRNA levels skeletal muscle
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in appetite
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in ad libitum food intake
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in food intake at home
timeFrame: Intervention period 1 and 2 (7 weeks apart)
measure: Change in fasting lipid oxidation rates
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in lipid oxidation rates from fasting to fed
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in glucose oxidation rates from fasting to fed
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in fasting glucose oxidation rates
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in fasting protein oxidation rates
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in protein oxidation rates from fasting to fed
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in ghrelin levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in LEAP-2 levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in GLP-1 levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in GIP levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in Glucose levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in Insulin levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in Glucagon levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in Gastrin levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in CCK levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in cortisol levels
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in FAP cells in skeletal muscle
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in FAP cells in adipose tissue
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in physical activity levels
timeFrame: Intervention period 1 and 2 (7 weeks apart)
measure: Change in IPAQ-7
timeFrame: Intervention period 1 and 2 (7 weeks apart)
measure: Change in sleep quality (measured)
timeFrame: Intervention period 1 and 2 (7 weeks apart)
measure: Change in sleep quality (reported)
timeFrame: Intervention period 1 and 2 (7 weeks apart)
measure: Change in sleep quality
timeFrame: Study day 1 and 2 (7 weeks apart)
measure: Change in HADS
timeFrame: Intervention period 1 and 2 (7 weeks apart)
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Endocrinology and Internal Medicine
state: State
Study officials:
affiliation: Aarhus University Hospital
name: Jens Otto L Jørgensen, Professor
role: STUDY_DIRECTOR
affiliation: Aarhus University Hospital
name: Simon B Hansen, MD
role: PRINCIPAL_INVESTIGATOR
References: