OPTIMISE: Optimization of Treatment and Management of Schizophrenia in Europe

Sponsor

Rene Kahn (Other)

Overall Status

Completed

CT.gov ID

NCT01248195

Collaborator

King's College London (Other), Technische Universität München (Other), University of Manchester (Other), Ludwig-Maximilians - University of Munich (Other)

479

Enrollment

Locations

Arms

Duration (Months)

18.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizophreniform Disorder Schizoaffective Disorder	Drug: Amisulpride open label Drug: 6-week amisulpride double blind treatment Drug: 6-week olanzapine double blind treatment Drug: 12-week clozapine open-label treatment Behavioral: Psychosocial intervention	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

479 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Optimization of Treatment and Management of Schizophrenia in Europe

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Apr 1, 2016

Actual Study Completion Date :

Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Phase I: 1 arm 'amisulpride open label' For 4 weeks, all patients will be treated with amisulpride open label.	Drug: Amisulpride open label 4-week open label amisulpride treatment
Active Comparator: Phase II: 'amisulpride double blind' 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'	Drug: 6-week amisulpride double blind treatment 6-week amisulpride double blind treatment
Active Comparator: Phase II 'olanzapine double blind' 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'	Drug: 6-week olanzapine double blind treatment 6-week olanzapine double blind treatment
Other: Phase III: 1 arm 'clozapine open label' 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'	Drug: 12-week clozapine open-label treatment 12-week clozapine open-label treatment
Experimental: 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.	Behavioral: Psychosocial intervention Psychosocial intervention
No Intervention: Psychosocial Intervention phase: 'TAU' 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 'Treatment as usual' arm.

Outcome Measures

Primary Outcome Measures

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.
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.
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).
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.
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.
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

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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Melbourne Neuropsychiatry Centre	Melbourne		Australia	3053
2	Department of Biological Psychiatry, Innsbruck University Clinics	Innsbruck		Austria	A-6020
3	Katholieke Universiteit Leuven (KU Leuven)	Leuven		Belgium	B - 3070
4	University Specialised Hospital for Active Treatment in Neurology and Psychiatry "St. Naum"	Sofia		Bulgaria	1113
5	Psychiatrické centrum Praha	Prague	Ustavni 91	Czechia	181 03 Praha 8-Bohnice
6	Psychiatrická klinika LF UK, Fakultní nemocnice	Hradec Králové		Czechia	CZ - 500 05
7	Center for Neuropsychiatric Research	Glostrup		Denmark	DK-2600
8	Institut National de la Santé et de la Reserche Médicale (INSERM)	Créteil Cedex		France	94010
9	Martin-Luther-University (MLU) of Halle-Wittenberg	Halle		Germany	06097
10	Deprtment of Psychiatry, University of Heidelberg	Mannheim		Germany	J 5, D-68159
11	Ludwig-Maximilians University München	München		Germany	80336
12	Technische Universität München (TUM)	München		Germany	81675
13	Sheba Medical Centre Department of Psychiatry	Tel Hashomer		Israel	52621
14	Department of Psychiatry University of Naples	Naples		Italy	80138
15	University Medical Center Utrecht	Utrecht		Netherlands	3584 CX
16	Department of Adult Psychiatry, University of Medical Sciences	Poznan		Poland	60-572
17	Obregia Psychiatric Hospital	Bucuresti		Romania	7000
18	Hospital Clinic i Provincial	Barcelona		Spain	08036 Barcelona
19	Servicio Madrileño de Salud (SERMAS)	Madrid		Spain	28007
20	Hospital Clínico San Carlos	Madrid		Spain	28040 Madrid
21	Instituto de Investigación Hospital 12 de Octubre	Madrid		Spain	28041 Madrid
22	Universidad de Oviedo	Oviedo		Spain	33011 Oviedo
23	Clienia Schlössli AG, Privatklinik für Psychiatrie und Psychotherapie	Oetwil am See		Switzerland	CH-8618
24	King's College London, Departments of Psychological Medicine, Psychiatry & Cognitive Neuroscience	London		United Kingdom	SE5 8AF
25	West London Mental Health Trust	London		United Kingdom	W12 0NN
26	University of Manchester	Manchester		United Kingdom	M13 9PL