Background: The synthetic glucocorticoid dexamethasone can induce serious neuropsychiatric adverse effects. Dexamethasone activates the glucocorticoid receptor (GR) but, unlike endogenous cortisol, not the mineralocorticoid receptor (MR). Moreover, dexamethasone suppresses cortisol production, thereby eliminating its MR binding. Consequently, GR overactivation combined with MR underactivation may contribute to the neuropsychiatric adverse effects of dexamethasone. The DEXA-CORT trial aims to re-activate the MR using cortisol to reduce neuropsychiatric adverse effects of dexamethasone treatment.

Methods and analysis: The DEXA-CORT study is a multi-centre, randomised, double-blind, placebo-controlled trial in adult patients who undergo elective brain tumour resection treated perioperatively with high doses of dexamethasone to minimize cerebral oedema. 180 patients are randomised between treatment with either twice daily 10mg hydrocortisone or placebo during dexamethasone treatment. The primary study outcome is the difference in proportion of patients scoring ≥3 points on at least one of the Brief Psychiatric Rating Scale questions 5 days postoperatively, or earlier at discharge. Secondary outcomes are neuropsychiatric symptoms, quality of sleep, health-related quality of life and neurocognitive functioning at several time points postoperatively. Furthermore, neuropsychiatric history, (serious) adverse events, prescribed (psychiatric) medication and referrals or evaluations of psychiatrist/psychologist, and laboratory measurements are assessed.

Ethics and dissemination: The study has been approved by the Medical Research Ethics Committee of the Leiden University Medical Center and by the Dutch competent authority. It is an investigator-initiated study with financial support by ZonMw and the Dutch Brain Foundation. Results of the study will be submitted for publication in a peer-reviewed journal.

Trial registration number: NL6726 (Netherlands Trial Register); open for patient inclusion. EudraCT number 2017-003705-17.