N.A.
Conditions
Interventions
In random order, subjects will receive 7.5 mg prednisolone for one week, directly followed by 30 mg of prednisolone for one week. After a washout period of 4 weeks (or by exception 8 weeks), subjects
Sponsors
N.A.
Eligibility
Inclusion criteria
Inclusion criteria: 1. Participants must be healthy with no relevant medical history (e.g. astma, solid organ transplantation, secondary adrenal insufficiency) and no use of medication. 2. Female participants aged <50 years must be using oral contraceptives and female participants age =50 years must be in the postmenopausal state 3. Command of the Dutch language 4. Providing written IC 5. BMI between 18.5 and 30 kg/m2 6. Participants must be between 18 and 75 years of age
Exclusion criteria
Exclusion criteria: 1. Potential participants who are unlikely to adhere to the study protocol (for instance subjects which have a history of substance abuse or non-compliance) 2. Potential participants with a medical history of: a. Diseases affecting the HPA-axis: e.g. primary and secondary adrenal insufficiency, pituitary tumors, and nightshift workers b. Diseases affecting the HPG-axis: e.g. Cushing disease. c. Chronic inflammatory diseases: e.g. rheumatoid arthritis, polymyalgia rheumatic, and asthma d. Psychiatric diseases e. Diabetes 3. Shift workers. 4. Potential participants with a kidney function <60 ml/min/1.73m2, abnormalities in liver enzymes, and/or abnormalities in thyroid function 5. Potential participants who are dependent on corticosteroids, e.g. asthmatic patients, and transplant recipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main study endpoint is the difference in total cortisol excretion as measured in 24h-urine at between the lower doses of prednisolone and dexamethasone as well as between and the higher doses of prednisolone and dexamethasone doses. | — |
Secondary
| Measure | Time frame |
|---|---|
| - The effect of a dosage increase from low dose to high dose prednisolone and from low dose to high dose dexamethasone on total cortisol excretion in 24h-urine. - Suppression of the HPA-axis measured by plasma cortisol, adrenocorticotropic hormone, and metabolites in the steroid profile in 24h-urine (e.g. free and total cortisol, tetrahydrocortisol, tetrahydrocortisone, and allo- tetrahydrocortisol). - Suppression of the HPG-axis measured by testosterone, LH, FSH, SHBG, dihydrotestosterone, and steroid profile in 24h-urine (e.g. androsterone, etiocholanolone, and dehydroepiandrosterone). - The pharmacokinetics and pharmacodynamics of prednisolone and dexamethasone. - Suppression of the immune system measured by leucocyte count, granulocyte count (neutrophils, eosinophil’s, and basophils), monocyte count, absolute B cell (CD19+) count, absolute T cell (CD3+, CD4+ and CD8+) count, absolute natural killer cell (CD16+ en CD56+) count, and RNA. - Renin–angiotensin–aldosterone system measured by plasma renin, aldosterone, potassium, 24h-urine potassium, and trans-tubular potassium gradient. - Muscle mass measured by 24h urinary creatinine excretion rate and creatine kinase. - Metabolic parameters measured by fasting glucose, fasting insulin, HbA1c, cholesterol, triglycerides, glycerol, and non-esterified fatty acids. - Bone parameters as measured by calcium and osteocalcin. - Clinical parameters: body weight, height, waist circumference, hip circumference, and blood pressure | — |
Contacts
Public ContactSuzanne Stam
University Medical Center Groningen
Outcome results
None listed