E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuropsychiatric adverse effects which can be caused by dexamethasone. For example delirium, anxiety, depression, mania and psychosis. But also cognitive impairment and sleep disturbance. |
Psychiatrische klachten die kunnen ontstaan bij dexamethason gebruik, zoals delier, angst, depressie, manie en psychoses. Ook cognitieve klachten en slaap klachten. |
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E.1.1.1 | Medical condition in easily understood language |
Neuropsychiatric adverse effects which can be caused by dexamethasone. For example delirium, anxiety, depression, mania and psychosis. But also cognitive impairment and sleep disturbance. |
Psychiatrische klachten die kunnen ontstaan bij dexamethason gebruik, zoals delier, angst, depressie, manie en psychoses. Ook cognitieve klachten en slaap klachten. |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate whether a low-dose of hydrocortisone (cortisol) reduces neuropsychiatric symptoms in glioma, meningioma and brain metastasis patients who are perioperatively treated with a high dose of the synthetic glucocorticoid dexamethasone, compared to patients treated with high dose dexamethasone alone. |
Ons doel is onderzoeken of hydrocortison de neuropsychiatrische bijwerkingen van dexamethason kan verminderen. |
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E.2.2 | Secondary objectives of the trial |
Investigate whether additional hydrocortisone improves sleep quality of neurosurgical patients treated with high dose dexamethasone. Investigate whether additional hydrocortisone improves quality of life of neurosurgical patients treated with high dose dexamethasone. Investigate whether additional hydrocortisone improves cognitive functioning of neurosurgical patients treated with high dose dexamethasone. Investigate whether a history of psychiatric problems predisposes for psychiatric problems during the use of dexamethasone. Investigate the short-term and long-term effects of hydrocortisone addition to dexamethasone. Verify MR targeting and study the molecular effects of hydrocortisone co-treatment in resected tumour specimens.
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Onderzoeken of hydrocortison de slaapkwaliteit, cognitief functioneren en kwaliteit van leven kan verbeteren. Ook of geschiedenis van psychische klachten voorspellend is voor het ontwikkelen van psychische klachten bij dexamethason gebruik. Onderzoeken van het korte en lange termijn effect van hydrocortison. En moleculaire effecten van hydrocortison onderzoeken in specimen uit het tumor weefsel. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Cranial glioma, meningioma or brain metastasis scheduled to undergo surgery (resection) Minimal dose of peri-operative cumulative dexamethasone exposure of 24mg or more in 6 days ≥18 years Good clinical condition; KPS ≥ 70 (see attachments 1) Life expectancy ≥ 6 months
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Craniale glioma, meningioma of hersenmetastase patiënten die een operatie ondergaan (resectie) Minimale dosis dexamethason rondom de operatie van 24mg of meer in 6 dagen ≥18 jaar Goede klinische conditie; KPS≥70 Levensverwachting ≥6 maanden |
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E.4 | Principal exclusion criteria |
Non-native speakers of Dutch or insufficient command of the Dutch language Patients that are unable to overview consequences of trial participation Patients with aphasia Patients that are not able to fill in the questionnaires because of cognitive impairments at the discretion of the physician Patients with psychiatric diseases or neurological deficits that interfere with the study to the judgement of treating physician
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Moedertaal niet Nederlands of onvoldoende beheersing van de Nederlandse taal Patiënten die de gevolgen van deelname aan de studie niet kunnen overzien Patiënten met afasie Patiënten die niet in staat zijn vragenlijsten in te vullen door cognitieve problemen, naar oordeel van de behandelend arts Patiënten met psychiatrische ziekten of neurologische gebreken die interfereren met de studie, naar oordeel van de behandelend arts
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E.5 End points |
E.5.1 | Primary end point(s) |
Neuropsychiatric adverse effects will be measured with the Brief Psychiatric Rating Scale (BPRS) version 4.0. The BPRS is a validated questionnaire, which provides a description of major symptom characteristics in psychiatric patients. It is developed as a rapid evaluation technique to assess treatment change, and available in Dutch. The BPRS covers the presence and seriousness of 24 symptoms scored on a 7 point scale (1=not present, 7=extremely severe). The total score is used and compared from one evaluation to the next to measure the response to treatment. |
De primaire uitkomstmaat is neuropsychiatrische bijwerkingen gemeten met de Brief Psychiatric Rating Scale (BPRS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The BPRS will be assessed three times: on an outpatient clinic appointment before surgery, at the day of discharge, and 5 - 8 weeks after surgery. |
De BPRS wordt drie keer afgenomen: tijdens een poli-afspraak voor de operatie, op de dag van ontslag, en 5 - 8 weken na de operatie. |
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E.5.2 | Secondary end point(s) |
Secondary parameters are neuropsychiatric adverse effects measured with different questionnaires (Hospital Anxiety and Depression Scale (HADS), Altman Self-Rating Mania scale (ASRM), Positive Affect Negative Affect Scale (PANAS), Delirium Observation Scale (DOS)); neurophysiological functioning assessed with different cognitive tests, sleep quality measured with the Leeds Sleep Evaluation Questionnaire (LSEQ) and quality of life with QLQ-C30+BN20. |
Secundaire uitkomstmaten zijn: neuropsychiatrische bijwerkingen gemeten met vragenlijsten (Hospital Anxiety and Depression Scale (HADS), Altman Self-Rating Mania scale (ASRM), Positive Affect Negative Affect Scale (PANAS), Delirium Observation Scale (DOS)); slaap kwaliteit gemeten met vragenlijst (Leeds Sleep Evaluation Questionnaire (LSEQ)); cognitie gemeten met cognitieve testen en kwaliteit van leven met QLQ-C30 + BN20 vragenlijst. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between day -14 and -2 before surgery: HADS, QoL, PANAS, LSEQ, ASRM (these questionnaires can be filled in at home). In addition: BPRS, cognitive tests, miniscreen on psychiatric background, NPI-Q and aphasia screening (when needed). During hospitalisation after surgery: nurses will fill in the DOS (in case of clinical psychiatric symptoms). Day of discharge: BPRS, LSEQ, MoCA, PANAS, NPI-Q and aphasia screening (when needed), and DOS by nurses (in case of clinical psychiatric symptoms). 2 weeks after surgery: HADS, PANAS, LSEQ, ASRM (filled in at home). 5 - 8 weeks after surgery: BPRS, cognitive tests, LSEQ, PANAS, NPI-Q. 3 months after surgery: HADS, QoL, PANAS, LSEQ, ASRM (filled in at home). |
Tussen dag -14 en -2 voor operatie op de dag van een poli-afspraak: HADS, QoL, PANAS, LSEQ, ASRM (vragenlijsten kunnen thuis ingevuld worden). Ook: BPRS, cognitieve testen, miniscreen voor psychiatrische achtergrond, NPI-Q en afasie screening (wanneer nodig). Gedurende opname in ziekenhuis na operatie: de verpleegkundigen zullen de DOS bijhouden (in geval van klinische psychiatrische symptomen). Dag van ontslag: BPRS, LSEQ, MoCA, PANAS, NPI-Q en afasie screening (wanneer nodig), en DOS door verpleegkundigen (in geval van klinische psychiatrische symptomen). 2 weken na operatie: HADS, PANAS, LSEQ, ASRM (thuis ingevuld). 5 - 8 weken na operatie: BPRS, cognitieve testen, LSEQ, PANAS, NPI-Q. 3 maanden na operatie: HADS, QoL, PANAS, LSEQ, ASRM (thuis ingevuld). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last patient hands in the last questionnaires. This is estimated at 29 January 2025. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |