E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
Depressive Störung |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
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 |
The main objective of this trial is to relate functional and structural MR parameters (e.g. local and system level BOLD signal, gray matter, functional and structural connectivity, surface and parcellation measures) to drug response and remission. |
Das Hauptziel dieser Studie stellt die Untersuchung des Zusammenhangs zwischen funktionellen und strukturellen MR Parametern (BOLD Signal, graue Substanz, funktionelle und strukturelle Konnektivität, Oberflächenmessungen) und Therapieansprechen sowie Remission dar. |
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E.2.2 | Secondary objectives of the trial |
A secondary objective of this trial is to relate genetic variation of SLC6A4, BDNF, HTR1A, NR3C1 and FKBP5 to neural markers of treatment response. An additional objective is to investigate the potential use of peripheral parameters such as mRNA transcription and protein expression levels of these genes as well as 5-HT uptake and cortisol levels as peripheral correlates of neural markers of drug response. |
Ein weiteres Ziel unserer Studie ist es zu untersuchen, ob diese neuronale Veränderungen in einem korrelativen Zusammenhang mit den peripheren Parametern wie RNA-Expression, Serotonin uptake, Serumprotein-basierte Parameter, und dem Cortisollevel stehen, und dass Genotypen, die in pharmakogenetischen Assoziationsstudien mit Therapieansprechen in Verbindung gebracht worden sind, das Antwortverhalten dieser Hirnstrukturen auf Escitalopramtherapie beeinflussen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- willingness and competence to sign the informed consent form voluntarily - aged 18 – 45 years - right-handedness - a DSM-IV diagnosis of a major depressive episode by a structured clinical interview (SCID) - a MADRS score ≥20 and ≤ 30 - ability to be managed as outpatients - ability to fulfill the criteria to undergo an MRI scan - Caucasian subjects of European ancestry
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- Einverständnis und Kompetenz die Patienteninformation zur freiwilligen Studienteilnahme zu unterzeichnen - Alter 18 – 45 Jahre - Rechtshändigkeit - Diagnose einer ggw. depressiven Episode einer Major Depression nach DSM-IV - Einen MADRS Wert ≥20 und ≤ 30 - ambulante Betreuung möglich - Durchführung einer MRT Messung möglich - Europäische Herkunft
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E.4 | Principal exclusion criteria |
- previous or concurrent major medical or neurological illness - clinically significant abnormal values in routine laboratory screening or general physical examination - DSM-IV diagnosis of substance dependence within the past year, except for caffeine or nicotine or current substance abuse - DSM-IV diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or an anxiety disorder as a primary diagnosis - the use of any psychotropic drug within the last two months - unresponsiveness of a former major depressive episode to an adequate antidepressive drug dosing of at least 6 weeks duration or any kind of therapy resistance - a history of severe drug allergy or hypersensitivity or known hypersensitivity to escitalopram - being acutely suicidal either indicated by a score ≥ 5 on item 10 (suicidal thoughts) on the MADRS or a score ≥ 4 on the HAM-D 21 (suicidal thoughts) or according to the investigator´s opinion - failures to comply with the study protocol or to follow the instructions of the investigating team - current pregnancy or breast feeding; - metallic implants or other contraindications to MRI
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- Momentane oder frühere schwere somatische, sowie neurologische Erkrankungen - Klinisch signifikante abnormale Werte in Routine Blutuntersuchung und/oder physikalischen Untersuchung - DSM-IV Diagnose einer Substanzabhängigkeit ausgenommen Koffein oder Nikotin (gegenwärtig oder während des letzten Jahres) - DSM-IV Diagnose einer Schizophrenie, einer schizoaffektiven Störung, einer Bipolaren Störung, oder einer Angsterkrankung als Primärdiagnose - Psychopharmakologische Behandlung innerhalb der letzten 2 Monate - Nicht-Ansprechen auf eine adäquate Dosierung eines Antidepressivum über einen Zeitraum von mind. 6 Wochen oder jegliche Art von Therapieresistenz - Schwere Arzneimittelallergie, oder bekannte Hypersensitivität für Escitalopram - Akute Suizidalität - ggw. Schwangerschaft oder Stillperiode - Metallische Implantate oder andere Kontraindikationen für MRI
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome variables are functional and structural MRI parameters dependent on drug response and remission. |
Primären Endzeitpunkt stellt die Abhängigkeit der funktionellen und strukturellen MRT Parameter von Therapieansprechen und Remission dar. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This endpoint will be evaluated 8 weeks after escitalopram treatment initiation. |
Dieser Endzeitpunkt wird 8 Wochen nach behandlungsbeginn mit Escitalopram evaluiert. |
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E.5.2 | Secondary end point(s) |
Secondary outcome variables will be genotype-mediated drug response and association between peripheral parameters (such as mRNA expression levels, serotonin uptake, cortisol levels) and drug response. |
Sekundären Endzeitpunkt stellt das von Genotypen beeinflusste Therapiensprechen und der Zusammenhang zwischen peripheren Parametern (mRNA Expression levels, serotonin uptake, cortisol levels) und Therapieansprechen dar. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
This endpoint will be evaluated 8 weeks after escitalopram treatment initiation. |
Dieser Endzeitpunkt wird 8 Wochen nach behandlungsbeginn mit Escitalopram evaluiert. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
pharmaco MRI |
Pharmaco MRI assesses the relation of functional and structural MR parameters to drug response and remission. |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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After the last MRT measurement which is planned when maximum response is achieved (after 8 weeks of treatment with escitalopram) patients undergo the end-of-study examination. The investigator must temporarily interrupt or permanently discontinue the study drug if continued administration is believed to be contrary to the best interests of the patient or for administrative reasons, in particular withdrawal of the patient’s consent.
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Die Nachuntersuchung erfolgt eine Woche nach der letzten MRT Messung, die in der 8. Woche nach Behandlungsbeginn geplant ist, da es zu diesem Zeitpunkt mit einem maximalen Therapieansprechen zu rechnen ist. Der behandelnder Arzt kann die Teilnahme an der Studie vorzeitig beenden, wenn er den Eindruck hat, dass eine weitere Teilnahme an der klinischen Prüfung nicht im Interesse der Patienten ist. Patienten haben die wahl ohne Grund zu nennen vorzeitig aus der klinischen Prüfung auszuscheiden. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |