The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone
Introduction 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, ther...
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2021-12-01
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| author | Elisabeth F C van Rossum Amir H Zamanipoor Najafabadi Wouter A Moojen Nienke R Biermasz Wouter R van Furth Onno C Meijer Clemens M F Dirven Anne-Sophie C A M Koning Djaina D Satoer Christiaan H Vinkers Rishi D S Nandoe Tewarie Alberto M Pereira |
| author_facet | Elisabeth F C van Rossum Amir H Zamanipoor Najafabadi Wouter A Moojen Nienke R Biermasz Wouter R van Furth Onno C Meijer Clemens M F Dirven Anne-Sophie C A M Koning Djaina D Satoer Christiaan H Vinkers Rishi D S Nandoe Tewarie Alberto M Pereira |
| author_sort | Elisabeth F C van Rossum |
| collection | DOAJ |
| description | Introduction 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 reactivate the MR using cortisol to reduce neuropsychiatric adverse effects of dexamethasone treatment.Methods and analysis The DEXA-CORT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients who undergo elective brain tumour resection treated perioperatively with high doses of dexamethasone to minimise cerebral oedema. 180 patients are randomised between treatment with either two times per day 10 mg 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 (BPRS) 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 protocol has been approved by the Medical Research Ethics Committee of the Leiden University Medical Center, and by the Dutch competent authority, and by the Institutional Review Boards of the participating sites. It is an investigator-initiated study with financial support by The Netherlands Organisation for Health Research and Development (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. |
| format | Article |
| id | doaj-art-5ade67313dc3462f8dcbaeecd7ae8f8c |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-12-01 |
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| spelling | doaj-art-5ade67313dc3462f8dcbaeecd7ae8f8c2024-12-10T15:25:09ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-054405The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasoneElisabeth F C van Rossum0Amir H Zamanipoor Najafabadi1Wouter A Moojen2Nienke R Biermasz3Wouter R van Furth4Onno C Meijer5Clemens M F Dirven6Anne-Sophie C A M Koning7Djaina D Satoer8Christiaan H Vinkers9Rishi D S Nandoe Tewarie10Alberto M Pereira11Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Neurosurgery, University Neurosurgical Center Holland, Leiden University Medical Center, Haaglanden Medical Center and Haga Teaching Hospitals, Leiden and The Hague, The NetherlandsNeurosurgery, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Medicine, Division of Endocrinology, and Centre for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, The NetherlandsDepartment of Neurosurgery, Leiden University Medical Center, Leiden, NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Neurosurgery, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands6 Neurosurgery, Erasmus Medical Center, Rotterdam, Zuid-Holland, The Netherlandsassistant professorDepartment of Neurosurgery, University Neurosurgical Center Holland, Leiden University Medical Center, Haaglanden Medical Center and Haga Teaching Hospitals, Leiden and The Hague, The NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The NetherlandsIntroduction 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 reactivate the MR using cortisol to reduce neuropsychiatric adverse effects of dexamethasone treatment.Methods and analysis The DEXA-CORT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients who undergo elective brain tumour resection treated perioperatively with high doses of dexamethasone to minimise cerebral oedema. 180 patients are randomised between treatment with either two times per day 10 mg 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 (BPRS) 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 protocol has been approved by the Medical Research Ethics Committee of the Leiden University Medical Center, and by the Dutch competent authority, and by the Institutional Review Boards of the participating sites. It is an investigator-initiated study with financial support by The Netherlands Organisation for Health Research and Development (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.https://bmjopen.bmj.com/content/11/12/e054405.full |
| spellingShingle | Elisabeth F C van Rossum Amir H Zamanipoor Najafabadi Wouter A Moojen Nienke R Biermasz Wouter R van Furth Onno C Meijer Clemens M F Dirven Anne-Sophie C A M Koning Djaina D Satoer Christiaan H Vinkers Rishi D S Nandoe Tewarie Alberto M Pereira The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone BMJ Open |
| title | The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone |
| title_full | The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone |
| title_fullStr | The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone |
| title_full_unstemmed | The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone |
| title_short | The DEXA-CORT trial: study protocol of a randomised placebo-controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone |
| title_sort | dexa cort trial study protocol of a randomised placebo controlled trial of hydrocortisone in patients with brain tumour on the prevention of neuropsychiatric adverse effects caused by perioperative dexamethasone |
| url | https://bmjopen.bmj.com/content/11/12/e054405.full |
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