Bioequivalence study of prednisolone and dexamethasone – The CORE study

Rationale: Corticosteroids are among the most important contributions to the medical field from the last century. Over the years, multiple new synthetic corticosteroids have been development and numerous studies have been performed, uncovering the important and beneficial anti-inflammatory and immunosuppressive characteristics of corticosteroids. Nowadays, corticosteroids are widely used in clinical practice, as their immunosuppressive characteristics are essential in treatment regimens for many chronic diseases, such as auto-immune diseases, lymphatic malignancies, and pulmonary diseases.
Unfortunately, to date, the efficacy data of corticosteroids are based on bioequivalency studies performed in the sixties and seventies of the last century, when randomized controlled trials (RCT) were rarely performed and not yet considered to be the golden standard. Prednisolone and dexamethasone are the two most widely used glucocorticoids. Their bioequivalence are estimated to be 1: 0.15, this is however, based on dated studies. Additionally, clinicians assume that all organ specific effects are similar between the different types of corticosteroids. However, according to recent insight, it could very well be that glucocorticoid sensitivity differs between variable tissues like the immune system, kidney, and brain. This is of importance as many clinicians, prescribe glucocorticoids in a standardized manner assuming that one size fits all. Yet, as there is a lack of modern era studies with a good quality, this is assumption may not be a justified approach.
Objective: 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.
Study design: A randomized, 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 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.

Due to the difference in mineralocorticoid characteristics between prednisolone and dexamethasone, it is hypothesized that dexamethasone will have a greater effect then prednisolone, especially when assessing neurocognitive function and blood pressure.

Duration of participation is 2 months.
Subjects will visit the UMC Groningen six times. Once for a screening visit, when included once for a baseline measurement, and four times for a study visit.

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.