Optimization of Treatment and Management of Schizophrenia in Europe
- Conditions
- SchizophreniaSchizophreniform DisorderSchizoaffective Disorder
- Interventions
- Registration Number
- NCT01248195
- Lead Sponsor
- Rene Kahn
- Brief Summary
The purpose of the study is optimising current treatments in schizophrenia and explore novel therapeutic options for schizophrenia. The study intends to both address basic, but so far unanswered, questions in the treatment of schizophrenia and develop new interventions. It is expected that the project will lead to evidence that is directly applicable to treatment guidelines, and will identify potential mechanisms for new drug development.
- Detailed Description
Despite nearly fifty years of pharmacological and psychosocial research, the overall prognosis of schizophrenia has improved only marginally. While the efficacy of most antipsychotic medication is generally uncontested, their overall functional impact has been modest. In order to improve this unsatisfactory result, this study aims to optimize current treatments in schizophrenia and explore novel therapeutic options for schizophrenia. The study comprises a medication intervention component, a psychosocial intervention component, a biological predictor component and an MRI component. MRI assessments are performed at baseline, and used to determine whether potential organic causes for psychotic symptoms are present, and to test prospective value of these assessments for subsequent treatment response. MRI assessments of healthy volunteers will be included to test for deviations in patients' assessments; these volunteers will not participate in any other protocol procedure. The medication intervention component comprises a first 4-week phase of amisulpride treatment. Non-responders will subsequently be randomised to a 6-week double blind phase on either amisulpride or olanzapine. Patients who classify as non-responders at the end of this phase, a 12-week open label treatment with clozapine is initiated. Patients who classify as a responder in phase I, II or III, are drop outs or who are non-responders at the end of phase III flow to the psychosocial intervention component of the study. During this part, several interventions are tested, aimed to increase treatment compliance and keep patients on the medication to which they've responded well. Through the biological predictor component, it is determined whether glutamatergic markers predict response to first and second line treatments, and if an empirical combination of pharmacogenetic, proteomics- and metabolomic markers can provide clinical valuable predictive value.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 479
- Diagnosis of schizophrenia as defined by DSM-IV-R as determined by the M.I.N.I.plus
- Age 18 or older.
- The first psychosis occurred at least one year and no more than 7 years ago.*
- If patients are using an antipsychotic drug, a medication switch is currently under consideration.
- Capable of providing written informed consent.
- Intolerance / hypersensitivity to one of the drugs (including active substances, metabolites and excipients) in this study including oral risperidone, paliperidone and aripiprazole and/or hypersensitivity to risperidone.
- Pregnancy or lactation.
- Patients who are currently using clozapine.
- Patients who do not fully comprehend the purpose or are not competent to make a rational decision whether or not to participate.
- Patients with a documented history of non-response and/or intolerance to any of the study medications and/or a documented history of non-response to a treatment with one of the study drugs of at least 6 weeks within the registered dose range.
- Forensic patients.
- Patients who have been treated with an investigational drug within 30 days prior to screening.
- Simultaneous participation in another intervention study (neither medication or psychosocial intervention).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase I: 1 arm 'amisulpride open label' Amisulpride open label For 4 weeks, all patients will be treated with amisulpride open label. Phase II: 'amisulpride double blind' 6-week amisulpride double blind treatment Patients who do not meet remission criteria during phase I (4 weeks open label amisulpride), flow to phase II where they are randomised to 1 of 2 6-week double blind treatment arms, one of which is 'amisulpride double blind' Phase II 'olanzapine double blind' 6-week olanzapine double blind treatment Patients who do not meet remission criteria during phase I (4 weeks open label amisulpride), flow to phase II where they are randomised to 1 of 2 6-week double blind treatment arms, one of which is 'olanzapine double blind' Phase III: 1 arm 'clozapine open label' 12-week clozapine open-label treatment Patients who do not meet remission criteria during phase II (6-week double blind amisulpride vs olanzapine), flow to phase III, where only 1 arm is available: 'clozapine open label' Psychosocial intervention Psychosocial intervention Patients who meet remission criteria during any of the phases of the medication component, patients who drop out of the medication component and patients who did not meet remission criteria at the end of the medication component, will flow to the psychosocial intervention component, where they are randomised to 1 of 2 arms, one of which is the 'Psychosocial Intervention' arm.
- Primary Outcome Measures
Name Time Method PANSS Jan 2016 Study consists of multiple components, each with their own objectives. For this (medication) component: number of patients in remission, based on PANSS scores (criteria of Andreasen et al.; 2005) after 4 weeks open label amisulpride, after 6 weeks double blind amisulpride or olanzapine and after 12 weeks of open label clozapine.
SOFAS global functioning jan 2016 Psychosocial intervention component, objective B: drug adherence rates as a function of standardized global functioning (SOFAS score after 1 year) following psychosocial intervention vs treatment as usual.
Sellwood rating scale Jan 2016 Psychosocial intervention component, objective A: drug adherence rates as a function of (standardized self report and) Sellwood rating scales after 12 and 52 weeks.
MRS measures jan 2016 Biological predictors component, objective B: using MRS scans, differences between responders and non-responders in regional glutamate levels a) at baseline and b) between baseline and after one month of treatment with amisulpiride.
Biological profile jan 2016 Biological predictors component, objective A: drug response (remission vs non-remission) as a function of biological profile, after 4 weeks, 10 weeks and 22 weeks (after each medication phase).
MRI assessments jan 2016 MRI component objective: the percentage of first episode patients that show radiological abnormalities suggestive of neurological disorders which may explain the occurrence of psychotic symptoms - measurement at baseline only.
- Secondary Outcome Measures
Name Time Method Biological markers jan 2016 Biological predictors component has multiple secondary objectives, most important one is the ability of biological markers to predict response to antipsychotic and treatment tolerability in schizophrenia, after 4, 10 and 22 weeks.
MRI assessments jan 2016 The ability of MRI to predict response to antipsychotic treatment in schizophrenia, after 4, 10 and 22 weeks.
All cause treatment discontinuation jan 2016 The different components of the study have their own secondary objectives:
Medication component has multiple secondary objectives, most important one is all-cause treatment discontinuation after 4 weeks, 10 weeks and 22 weeks. Number and reason for premature discontinuations (treatment discontinuation) of the amisulpride and the olanzapine group will be compared (after 10 weeks).All cause discontinuation jan 2016 Psychosocial intervention component has multiple secondary objectives, most important one is all-cause treatment discontinuation between treatment groups after 12 and 52 weeks.
Trial Locations
- Locations (26)
Center for Neuropsychiatric Research
🇩🇰Glostrup, Denmark
Psychiatrické centrum Praha
🇨🇿Prague, Ustavni 91, Czechia
Ludwig-Maximilians University München
🇩🇪München, Germany
Melbourne Neuropsychiatry Centre
🇦🇺Melbourne, Australia
Instituto de Investigación Hospital 12 de Octubre
🇪🇸Madrid, Spain
Department of Biological Psychiatry, Innsbruck University Clinics
🇦🇹Innsbruck, Austria
Department of Psychiatry University of Naples
🇮🇹Naples, Italy
Technische Universität München (TUM)
🇩🇪München, Germany
Psychiatrická klinika LF UK, Fakultnà nemocnice
🇨🇿Hradec Králové, Czechia
Deprtment of Psychiatry, University of Heidelberg
🇩🇪Mannheim, Germany
Institut National de la Santé et de la Reserche Médicale (INSERM)
🇫🇷Créteil Cedex, France
Servicio Madrileño de Salud (SERMAS)
🇪🇸Madrid, Spain
University Specialised Hospital for Active Treatment in Neurology and Psychiatry "St. Naum"
🇧🇬Sofia, Bulgaria
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
West London Mental Health Trust
🇬🇧London, United Kingdom
Department of Adult Psychiatry, University of Medical Sciences
🇵🇱Poznan, Poland
King's College London, Departments of Psychological Medicine, Psychiatry & Cognitive Neuroscience
🇬🇧London, United Kingdom
Universidad de Oviedo
🇪🇸Oviedo, Spain
Hospital ClÃnico San Carlos
🇪🇸Madrid, Spain
Martin-Luther-University (MLU) of Halle-Wittenberg
🇩🇪Halle, Germany
University of Manchester
🇬🇧Manchester, United Kingdom
Katholieke Universiteit Leuven (KU Leuven)
🇧🇪Leuven, Belgium
Obregia Psychiatric Hospital
🇷🇴Bucuresti, Romania
Sheba Medical Centre Department of Psychiatry
🇮🇱Tel Hashomer, Israel
Clienia Schlössli AG, Privatklinik für Psychiatrie und Psychotherapie
🇨ðŸ‡Oetwil am See, Switzerland
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands