E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute suicidality, which is a rapid increase in suicidal ideation or behaviour from the patient's 'baseline' in the last 24 hours. |
Acute suïcidaliteit, gedefinieerd als een snelle toename in suïcidale gedachten of gedrag vanaf de 'baseline' van patiënt. |
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E.1.1.1 | Medical condition in easily understood language |
Acute suicidality, thoughts about the wish to kill oneself, or behaviour with either the aim to die or a significant likelyhood that one could die because of this behaviour. |
Acute suïcidaliteit, gedachten over de wens zichzelf van het leven te willen beroven, of gedrag met het doel te sterven of met een grote waarschijnlijkheid dat men als gevolg van het gedrag sterft |
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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 |
Primary Objective To investigate the anti-suicidal effects of a single dose of intranasal ketamine in acutely suicidal subjects.
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Het onderzoeken van het antisuïcidale effect van een eenmalige dosering van intranasale ketamine in acuut suïcidale proefpersonen. |
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E.2.2 | Secondary objectives of the trial |
to assess - the safety, - the antidepressant effects, - time-course of the effects - find neurobiological markers that predict and are associated with the response to ketamine using o hippocampal magnetic resonance spectroscopy (MRS) o structural connectivity using diffusion tensor imaging (DTI) o functional connectivity using magnetic resonance imaging (fMRI) o Blood samples
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het onderzoeken van - de veiligheid - het antidepressieve effect - het tijdsverloop van de efecten - het vinden van neurobiologische markers die de respons op ketamine voorspellen en/of daarmee geassocieerd zijn.
- het uitvoeren van hippocampaal magnetic resonance spectroscopy (MRS) - het verrichten van structureel connectiviteitsonderzoek met diffusion tensor imaging (DTI) - het onderzoeken van functionele connectiviteit middels functionele magnetic resonance imaging (fMRI)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Acute suicidality A Beck Scale for Suicide Ideation (BSSI)-score of 7 or above Subjects are in the age of 18-70
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acute suïcidaliteit een BSSI-score van 7 of hoger Proefpersonen zijn 18 tot 70 jaar oud.
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E.4 | Principal exclusion criteria |
-Psychosis -A diagnosis of schizophrenia or another psychotic disorder -A history of PCP- or ketamine addiction -Being under influence of GHB -A blood alcohol concentration (BAC)of >0.05% -A clinically significant and unstable cardiovascular, gastro-intestinal, pulmonal, renal, hepatic, endocrine or haematological disorder, a myocardial infarction, miction problems or a complex surgical problem that needs immediate attention -A known hypersensitivity for ketamine -Concomitant use of seligiline -Severe nose congestion or nasal polyps -Pregnancy or giving breastfeeding -Women using unreliable contraception -Being unable to answer the questionnaires -Being unwilling or unable to provide informed consent -Earlier participation in this study
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-Psychose -Een diagnose van schizofrenie of een andere psychotische stoornis -Een geschiedenis van PCP- of ketamineverslaving/misbruik -Onder invloed zijn van GHB -Een bloed alcohol concentratie (BAC) van >0,05% -Een klinisch significante en onstabiele cardiovasculaire, gastro-intestinale, pulmonale, renale, hepatische, endocriene of hematologische stoornis, een myocardinfarct, mictieproblemen of een complex chirurgisch probleem dat onmiddellijke medische aandacht behoeft. -Een bekende hypersensitiviteit voor ketamine. -Gelijktijdig gebruik van seligiline -Ernstige neusverstopping of neuspoliepen -Zwangerschap of het geven van borstvoeding -Vrouwen die geen betrouwbare anticonceptie gebruiken. -Niet in staat zijn vragenlijsten in te vullen/te beantwoorden -Niet willen of niet in staat zijn tot het geven van informed consent -Eerdere deelname aan de studie.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in suicidality scores on the BSSI between baseline and 180 minutes after 50 mg intranasal ketamine administration compared to 4.5 mg intranasal midazolam (placebo). |
Verandering in acute suïcidaliteit als gemeten met de Beck Scale for Suicide Ideation (BSSI), 180 minuten na 50mg intranasale ketamine, ten opzichte van 4,5mg intranasale midazolam. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Acute suicidality from baseline to 60 minutes, 180 minutes, one day, three days and one week after one intranasal ketamine administration compared to placebo, as measured with: a. Beck Scale for Suicide Ideation (BSSI) b. Sheehan Suicidality Tracking Scale (SSTS) c. Suicidality item on the Montgomery Asberg Depression Rating Scale. (MADRS). 2. Actual number of suicides and suicidal acts in both groups. 3. Depressive symptoms as measured with the MADRS from baseline to 60 minutes and 180 minutes, one day, three days and one week after one intranasal ketamine administration compared to placebo (34). 4. Psychotomimetic symptoms, as measured with the Brief Psychiatric Rating Scale – Positive Subscale (BPRS) from baseline to 60 minutes and 180 minutes. 5. Change in BDNF concentration, genetics and other biomarkers. A blood sample of 5ml will be taken by venepuncture into vacuum tubes containing ethylene diamine tetraacetic acid (EDTA) and be transferred into a heparinised tube, at baseline and at 180 minutes after ketamine/midazolam administration.
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1. Acute suïcidaliteit ten opzichte van baseline op 60 minuten, 180 minuten, één dag, drie dagen en één week na toediening van intranasale ketamine in vergelijking met placebo, gemeten met -de BSSI -de Sheehan Suicidality Tracking Scale (SSTS) -het suïcidaliteitsitem op de Montgomery Asberg Depression Rating Scale (MADRS). 2. Het aantal suïcides in beide groepen. 3. Depressieve symptomen als gemeten met de MADRS t.o.v. baseline op 60 minuten, 180 minuten, 1 dag, 3 dagen en 1 week na toediening van de intranasale ketamine. 4. Psychotomimetische symptomen als gemeten met de Brief Psychiatric Ratings Scale, Positive Subscale (BPRS-PS) t.o.v. baseline op 60 en 180 minuten na toediening. 5. Verandering in BDNF-concentratie, genetica en andere biomarkers. Middels venapunctie zal een bloedmonster van 5ml afgenomen worden in een met ethylene diamine tetraacetic acid (EDTA). Dit zal vervolgens in een gehepariniseerde buis overgebracht worden. Dit zal net voor de toediening en 180 minuten na de toediening van de ketamine dan wel de midazolam gebeuren. 6. Structural MRI, functional MRI (fMRI), diffusion tensor imaging (DTI), H-MRS-analysis of glutamate in hippocampus and prefrontal cortex. Subjects that were administered ketamine will be compared to subjects that were administered midazolam, at one day after administration. 7. A responder/non responder analysis. (Response is defined as a 50% reduction in BSSI-score). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
60 minutes, 180 minutes, 1 day, 3 days and 1 week after ketamine administration |
60 minuten, 180 minuten, 1 dag, 3 dagen en 1 week na ketaminetoediening |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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 | No |
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 last follow-up call of the last subject (one week after his/her visit) |
Het laatste telefoontje naar de laatst geïncludeerde proefpersoon (1 week na inclusie) |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |