Clinical trial NCT01248195: Optimization of Treatment and Management of Schizophrenia in Europe
Official title: Optimization of Treatment and Management of Schizophrenia in Europe
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizophreniform Disorder
Schizoaffective Disorder
Keywords: Schizophrenia
Schizophreniform disorder
Schizoaffective disorder
Imaging
Prognosis
Treatment guidelines
Pharmacogenetics
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: King's College London
name: Technical University of Munich
name: University of Manchester
name: Ludwig-Maximilians - University of Munich
First posted: 2010-11-25
Enrollment: 479
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of schizophrenia as defined by DSM-IV-R as determined by the M.I.N.I.plus
2. Age 18 or older.
3. The first psychosis occurred at least one year and no more than 7 years ago.\*
4. If patients are using an antipsychotic drug, a medication switch is currently under consideration.
5. Capable of providing written informed consent.

Exclusion Criteria:

1. 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.
2. Pregnancy or lactation.
3. Patients who are currently using clozapine.
4. Patients who do not fully comprehend the purpose or are not competent to make a rational decision whether or not to participate.
5. 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.
6. Forensic patients.
7. Patients who have been treated with an investigational drug within 30 days prior to screening.
8. Simultaneous participation in another intervention study (neither medication or psychosocial intervention).

Primary outcomes:
measure: PANSS
timeFrame: Jan 2016
measure: Sellwood rating scale
timeFrame: Jan 2016
measure: Biological profile
timeFrame: jan 2016
measure: MRS measures
timeFrame: jan 2016
measure: SOFAS global functioning
timeFrame: jan 2016
measure: MRI assessments
timeFrame: jan 2016
Secondary outcomes:
measure: All cause treatment discontinuation
timeFrame: jan 2016
measure: All cause discontinuation
timeFrame: jan 2016
measure: Biological markers
timeFrame: jan 2016
measure: MRI assessments
timeFrame: jan 2016
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Melbourne Neuropsychiatry Centre
city: Innsbruck
country: Austria
facility: Department of Biological Psychiatry, Innsbruck University Clinics
city: Leuven
country: Belgium
facility: Katholieke Universiteit Leuven (KU Leuven)
city: Sofia
country: Bulgaria
facility: University Specialised Hospital for Active Treatment in Neurology and Psychiatry "St. Naum"
city: Prague
country: Czechia
facility: Psychiatrické centrum Praha
state: Ustavni 91
city: Hradec Králové
country: Czechia
facility: Psychiatrická klinika LF UK, Fakultní nemocnice
city: Glostrup
country: Denmark
facility: Center for Neuropsychiatric Research
city: Créteil Cedex
country: France
facility: Institut National de la Santé et de la Reserche Médicale (INSERM)
city: Halle
country: Germany
facility: Martin-Luther-University (MLU) of Halle-Wittenberg
city: Mannheim
country: Germany
facility: Deprtment of Psychiatry, University of Heidelberg
city: München
country: Germany
facility: Ludwig-Maximilians University München
city: München
country: Germany
facility: Technische Universität München (TUM)
city: Tel Hashomer
country: Israel
facility: Sheba Medical Centre Department of Psychiatry
city: Naples
country: Italy
facility: Department of Psychiatry University of Naples
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Poznan
country: Poland
facility: Department of Adult Psychiatry, University of Medical Sciences
city: Bucuresti
country: Romania
facility: Obregia Psychiatric Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Madrid
country: Spain
facility: Servicio Madrileño de Salud (SERMAS)
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Instituto de Investigación Hospital 12 de Octubre
city: Oviedo
country: Spain
facility: Universidad de Oviedo
city: Oetwil am See
country: Switzerland
facility: Clienia Schlössli AG, Privatklinik für Psychiatrie und Psychotherapie
city: London
country: United Kingdom
facility: King's College London, Departments of Psychological Medicine, Psychiatry & Cognitive Neuroscience
city: London
country: United Kingdom
facility: West London Mental Health Trust
city: Manchester
country: United Kingdom
facility: University of Manchester
Study officials:
affiliation: University Medical Center Utrecht, the Netherlands
name: René Kahn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fraguas D, Diaz-Caneja CM, Pina-Camacho L, Winter van Rossum I, Baandrup L, Sommer IE, Glenthoj B, Kahn RS, Leucht S, Arango C. The role of depression in the prediction of a "late" remission in first-episode psychosis: An analysis of the OPTiMiSE study. Schizophr Res. 2021 May;231:100-107. doi: 10.1016/j.schres.2021.03.010. Epub 2021 Apr 7.
citation: Pollak TA, Vincent A, Iyegbe C, Coutinho E, Jacobson L, Rujescu D, Stone J, Jezequel J, Rogemond V, Jamain S, Groc L, David A, Egerton A, Kahn RS, Honnorat J, Dazzan P, Leboyer M, McGuire P. Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis. Biol Psychiatry. 2021 Jul 1;90(1):9-15. doi: 10.1016/j.biopsych.2020.11.014. Epub 2020 Nov 24.
citation: Kahn RS, Winter van Rossum I, Leucht S, McGuire P, Lewis SW, Leboyer M, Arango C, Dazzan P, Drake R, Heres S, Diaz-Caneja CM, Rujescu D, Weiser M, Galderisi S, Glenthoj B, Eijkemans MJC, Fleischhacker WW, Kapur S, Sommer IE; OPTiMiSE study group. Amisulpride and olanzapine followed by open-label treatment with clozapine in first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three-phase switching study. Lancet Psychiatry. 2018 Oct;5(10):797-807. doi: 10.1016/S2215-0366(18)30252-9. Epub 2018 Aug 13.