Clinical trial NCT04733144: Bioequivalence Study of Prednisolone and Dexamethasone
Official title: An Bioequivalence Study of Prednisolone and Dexamethasone; Corticosteroids Revised - The CORE Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2021-02-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Suppression of the hypothalamic-pituitary-adrenal axis - low dose
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-adrenal axis - high dose
timeFrame: 1 week per treatment
Secondary outcomes:
measure: Changes in hypothalamic-pituitary-adrenal axis suppression - 1
timeFrame: 1 week per treatment
measure: Changes in hypothalamic-pituitary-adrenal axis suppression - 2
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-adrenal axis - plasma cortisol
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-adrenal axis - ACTH
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-adrenal axis - metabolites of the 24h-urine steroid profile
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-gonadal axis - androgen profile
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-gonadal axis - gonadotropins
timeFrame: 1 week per treatment
measure: Suppression of the hypothalamic-pituitary-gonadal axis - metabolites of the 24h-urine steroid profile
timeFrame: 1 week per treatment
measure: Pharmacokinetics
timeFrame: 1 week per treatment
measure: Suppression of the immune system - granulocyte count
timeFrame: 1 week per treatment
measure: Suppression of the immune system - PBMCs
timeFrame: 1 week per treatment
measure: Effect on blood pressure
timeFrame: 1 week per treatment
measure: Effect on the Renin-angiotensin-aldosterone system - plasma renin
timeFrame: 1 week per treatment
measure: Effect on the Renin-angiotensin-aldosterone system - aldosterone
timeFrame: 1 week per treatment
measure: Effect on the Renin-angiotensin-aldosterone system - plasma potassium
timeFrame: 1 week per treatment
measure: Effect on the Renin-angiotensin-aldosterone system - 24h-urine potassium
timeFrame: 1 week per treatment
measure: Effect on the Renin-angiotensin-aldosterone system - trans-tubular potassium gradient
timeFrame: 1 week per treatment
measure: Metabolic parameters - OGTT
timeFrame: 1 week per treatment
measure: Metabolic parameters - lipid profile
timeFrame: 1 week per treatment
measure: Metabolic parameters - NEFAs
timeFrame: 1 week per treatment
measure: Muscle mass
timeFrame: 1 week per treatment
measure: Muscle strength
timeFrame: 1 week per treatment
measure: Clinical parameters - Weight
timeFrame: 1 week per treatment
measure: Clinical parameters - Body Mass Index (BMI)
timeFrame: 1 week per treatment
measure: Clinical parameters - Waist circumference
timeFrame: 1 week per treatment
measure: Clinical parameters - Hip circumference
timeFrame: 1 week per treatment
measure: Questionnaires - Quality of life
timeFrame: 1 week per treatment
measure: (Serious) Adverse Events
timeFrame: 1 week per treatment
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: André P. van Beek, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Groningen
name: Stephan J.L. Bakker, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stam SP, Vulto A, Vos MJ, Kerstens MN, Rutgers A, Kema I, Touw DJ, Bakker SJ, van Beek AP. Rationale and design of the CORE (COrticosteroids REvised) study: protocol. BMJ Open. 2022 Apr 26;12(4):e061678. doi: 10.1136/bmjopen-2022-061678.