Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to compare two different glucocorticoids, prednisolone and dexamethasone at two different doses for their organ specific effects, utilizing modern day standards.
Detailed description
Study design: A randomised, double blind, cross-over clinical trial. Study population: healthy human adult volunteers including 12 males and 12 females aged 18-75 years old. Intervention: 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 will receive 1,125 mg dexamethasone for one week, directly followed by 4,5 mg dexamethasone for one week. Main study parameters/endpoints: The main study endpoint is the difference in total urinary cortisol excretion as measured in 24h-urine between the lower doses of prednisolone and dexamethasone as well as between the higher doses of prednisolone and dexamethasone.
Interventions
DRUGPrednisolone
7,5 mg prednisolone (low dose) 30 mg prednisolone (high dose)
DRUGDexamethasone
1,125 mg dexamethasone 4,5 mg dexamethasone
Sponsors
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants must be healthy with no relevant medical history and no use of medication. * Female participants aged \<50 years must be using oral contraceptives and female participants age ≥50 years must be in the postmenopausal state * Command of the Dutch language * Providing written IC * BMI between 18.5 and 30 kg/m2 * Participants must be between 18 and 75 years of age
Exclusion criteria
* Potential participants who are unlikely to adhere to the study protocol (for instance subjects which have a history of substance abuse or non-compliance) * Potential participants with a medical history of: 1. Diseases affecting the HPA-axis: e.g. primary and secondary adrenal insufficiency, pituitary tumors, and nightshift workers 2. Diseases affecting the HPG-axis: e.g. Cushing disease. 3. Chronic inflammatory diseases: e.g. rheumatoid arthritis, polymyalgia rheumatic, and asthma 4. Psychiatric diseases 5. Diabetes * Shift workers * Potential participants with a kidney function \<60 ml/min/1.73m2, abnormalities in liver enzymes, and/or abnormalities in thyroid function * Potential participants who are dependent on corticosteroids, e.g. asthmatic patients, and transplant recipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Suppression of the hypothalamic-pituitary-adrenal axis - low dose | 1 week per treatment | Difference in HPA-axis suppression as measured by the difference of total urinary cortisol excretion in 24h-urine between 7,5 mg prednisolone and 1,125 mg dexamethasone |
| Suppression of the hypothalamic-pituitary-adrenal axis - high dose | 1 week per treatment | Difference of total urinary cortisol excretion in 24h-urine between 30 mg prednisolone (preceded by 7,5 mg prednisolone for one week) and 4,5 mg dexamethasone (preceded by 1,125 mg dexamethasone for one week) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Suppression of the hypothalamic-pituitary-adrenal axis - plasma cortisol | 1 week per treatment | The between-group difference in plasma cortisol levels |
| Suppression of the hypothalamic-pituitary-adrenal axis - ACTH | 1 week per treatment | The between-group difference in adrenocorticotropic hormone levels |
| Suppression of the hypothalamic-pituitary-adrenal axis - metabolites of the 24h-urine steroid profile | 1 week per treatment | The between-group difference in metabolites of the 24h-urine steroid profile |
| Suppression of the hypothalamic-pituitary-gonadal axis - androgen profile | 1 week per treatment | The between-group difference in androgen profiles |
| Suppression of the hypothalamic-pituitary-gonadal axis - gonadotropins | 1 week per treatment | The between-group difference in luteinizing hormone and follicle stimulating hormone |
| Suppression of the hypothalamic-pituitary-gonadal axis - metabolites of the 24h-urine steroid profile | 1 week per treatment | The between-group difference in metabolites of the 24h-urine steroid profile |
| Pharmacokinetics | 1 week per treatment | Area under the curve |
| Suppression of the immune system - granulocyte count | 1 week per treatment | The between-group difference in granulocyte count |
| Suppression of the immune system - PBMCs | 1 week per treatment | The between-group difference in peripheral blood mononuclear cell count |
| Effect on blood pressure | 1 week per treatment | The between-group difference in systolic and diastolic blood pressure |
| Effect on the Renin-angiotensin-aldosterone system - plasma renin | 1 week per treatment | The between-group difference in plasma renin |
| Effect on the Renin-angiotensin-aldosterone system - aldosterone | 1 week per treatment | The between-group difference in aldosterone |
| Effect on the Renin-angiotensin-aldosterone system - plasma potassium | 1 week per treatment | The between-group difference in plasma potassium |
| Changes in hypothalamic-pituitary-adrenal axis suppression - 1 | 1 week per treatment | Effect of a dosage increase from low dose to high dose prednisolone on total urinary cortisol excretion in 24h-urine |
| Effect on the Renin-angiotensin-aldosterone system - trans-tubular potassium gradient | 1 week per treatment | The between-group difference in trans-tubular potassium gradient |
| Metabolic parameters - OGTT | 1 week per treatment | The between-group difference in oral glucose tolerence tests |
| Metabolic parameters - lipid profile | 1 week per treatment | The between-group difference in lipid profile |
| Metabolic parameters - NEFAs | 1 week per treatment | The between-group difference in non-esterified fatty acids |
| Muscle mass | 1 week per treatment | The between-group difference in 24h urinary creatinine excretion rate |
| Muscle strength | 1 week per treatment | The between-group difference in handgrip strength |
| Clinical parameters - Weight | 1 week per treatment | The between-group difference in weight in kg |
| Clinical parameters - Body Mass Index (BMI) | 1 week per treatment | The between-group difference in BMI in kg/m2 |
| Clinical parameters - Waist circumference | 1 week per treatment | The between-group difference in waist circumference in cm |
| Clinical parameters - Hip circumference | 1 week per treatment | The between-group difference in hip circumference in cm |
| Questionnaires - Quality of life | 1 week per treatment | The between-group difference in quality of life, measured using the 36-Item Short Form Health Survey (SF-36). The score ranges from 0-100, with lower scores indicating a worse health status. |
| (Serious) Adverse Events | 1 week per treatment | The between-group difference in (serious) adverce events |
| Effect on the Renin-angiotensin-aldosterone system - 24h-urine potassium | 1 week per treatment | The between-group difference in 24h-urine potassium |
| Changes in hypothalamic-pituitary-adrenal axis suppression - 2 | 1 week per treatment | Effect of a dosage increase from low dose to high dose dexamethasone on total urinary cortisol excretion in 24h-urine |
Countries
Netherlands
Contacts
Primary ContactSuzanne P. Stam, MD
Outcome results
None listed