Optimization of Treatment and Management of Schizophrenia in Europe

Schizophrenia Clinical Trial

— OPTIMISE  

Official title:

Optimization of Treatment and Management of Schizophrenia in Europe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01248195
• Other study ID #: KP7242114
• Secondary ID: 2010-020185-19
• Status: Completed
• Phase: Phase 4
• Start date: May 2011
• Est. completion date: April 2016

Study information

• Verified date: May 2018
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 479
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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).

Related Conditions & MeSH terms

• Disease
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophreniform Disorder

Intervention

Drug:
• Amisulpride open label
4-week open label amisulpride treatment
• 6-week amisulpride double blind treatment
6-week amisulpride double blind treatment
• 6-week olanzapine double blind treatment
6-week olanzapine double blind treatment
• 12-week clozapine open-label treatment
12-week clozapine open-label treatment

Behavioral:
• Psychosocial intervention
Psychosocial intervention

Locations

Country	Name	City	State
Australia	Melbourne Neuropsychiatry Centre	Melbourne
Austria	Department of Biological Psychiatry, Innsbruck University Clinics	Innsbruck
Belgium	Katholieke Universiteit Leuven (KU Leuven)	Leuven
Bulgaria	University Specialised Hospital for Active Treatment in Neurology and Psychiatry "St. Naum"	Sofia
Czechia	Psychiatrická klinika LF UK, Fakultní nemocnice	Hradec Králové
Czechia	Psychiatrické centrum Praha	Prague	Ustavni 91
Denmark	Center for Neuropsychiatric Research	Glostrup
France	Institut National de la Santé et de la Reserche Médicale (INSERM)	Créteil Cedex
Germany	Martin-Luther-University (MLU) of Halle-Wittenberg	Halle
Germany	Deprtment of Psychiatry, University of Heidelberg	Mannheim
Germany	Ludwig-Maximilians University München	München
Germany	Technische Universität München (TUM)	München
Israel	Sheba Medical Centre Department of Psychiatry	Tel Hashomer
Italy	Department of Psychiatry University of Naples	Naples
Netherlands	University Medical Center Utrecht	Utrecht
Poland	Department of Adult Psychiatry, University of Medical Sciences	Poznan
Romania	Obregia Psychiatric Hospital	Bucuresti
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Instituto de Investigación Hospital 12 de Octubre	Madrid
Spain	Servicio Madrileño de Salud (SERMAS)	Madrid
Spain	Universidad de Oviedo	Oviedo
Switzerland	Clienia Schlössli AG, Privatklinik für Psychiatrie und Psychotherapie	Oetwil am See
United Kingdom	King's College London, Departments of Psychological Medicine, Psychiatry & Cognitive Neuroscience	London
United Kingdom	West London Mental Health Trust	London
United Kingdom	University of Manchester	Manchester

Sponsors (5)

Lead Sponsor	Collaborator
Rene Kahn	King's College London, Ludwig-Maximilians - University of Munich, Technische Universität München, University of Manchester

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Bulgaria,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Romania,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PANSS	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.	Jan 2016
Primary	Sellwood rating scale	Psychosocial intervention component, objective A: drug adherence rates as a function of (standardized self report and) Sellwood rating scales after 12 and 52 weeks.	Jan 2016
Primary	Biological profile	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).	jan 2016
Primary	MRS measures	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.	jan 2016
Primary	SOFAS global functioning	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.	jan 2016
Primary	MRI assessments	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.	jan 2016
Secondary	All cause treatment discontinuation	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).	jan 2016
Secondary	All cause discontinuation	Psychosocial intervention component has multiple secondary objectives, most important one is all-cause treatment discontinuation between treatment groups after 12 and 52 weeks.	jan 2016
Secondary	Biological markers	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.	jan 2016
Secondary	MRI assessments	The ability of MRI to predict response to antipsychotic treatment in schizophrenia, after 4, 10 and 22 weeks.	jan 2016

External Links

•   Study website