Optimization of Treatment and Management of Schizophrenia in Europe

NCT01248195 | Completed Phase 4 DMC

• 2 other identifiers: KP72421142010-020185-19
• Study Type: interventional
• Target: 479
• Locations: 15 countries
• Sites: 25

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.

Conditions

Schizophrenia; Schizophreniform Disorder; Schizoaffective Disorder

Keywords

Schizophrenia; Schizophreniform disorder; Schizoaffective disorder; Imaging; Prognosis; Treatment guidelines; Pharmacogenetics

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (4)

• All cause treatment discontinuation

  jan 2016

• All cause discontinuation

  jan 2016

• Biological markers

  jan 2016

• MRI assessments

  jan 2016

Study Arms (6)

Phase I: 1 arm 'amisulpride open label'

OTHER

For 4 weeks, all patients will be treated with amisulpride open label.

Drug: Amisulpride open label

Phase II: 'amisulpride double blind'

ACTIVE COMPARATOR

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

Phase II 'olanzapine double blind'

ACTIVE COMPARATOR

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

Phase III: 1 arm 'clozapine open label'

OTHER

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

Psychosocial intervention

EXPERIMENTAL

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 phase: 'TAU'

NO 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 'Treatment as usual' arm.

Interventions

Amisulpride open label DRUG

4-week open label amisulpride treatment

Phase I: 1 arm 'amisulpride open label'

6-week amisulpride double blind treatment DRUG

6-week amisulpride double blind treatment

Phase II: 'amisulpride double blind'

6-week olanzapine double blind treatment DRUG

6-week olanzapine double blind treatment

Phase II 'olanzapine double blind'

12-week clozapine open-label treatment DRUG

12-week clozapine open-label treatment

Phase III: 1 arm 'clozapine open label'

Psychosocial intervention BEHAVIORAL

Psychosocial intervention

Psychosocial intervention

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Rene Kahn: lead
• King's College London: collaborator
• Technical University of Munich: collaborator
• University of Manchester: collaborator
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (26)

Melbourne Neuropsychiatry Centre

Melbourne, 3053, Australia

Location

Department of Biological Psychiatry, Innsbruck University Clinics

Innsbruck, A-6020, Austria

Location

Katholieke Universiteit Leuven (KU Leuven)

Leuven, B - 3070, Belgium

Location

University Specialised Hospital for Active Treatment in Neurology and Psychiatry "St. Naum"

Sofia, 1113, Bulgaria

Location

Psychiatrické centrum Praha

Prague, Ustavni 91, 181 03 Praha 8-Bohnice, Czechia

Location

Psychiatrická klinika LF UK, Fakultní nemocnice

Hradec Králové, CZ - 500 05, Czechia

Location

Center for Neuropsychiatric Research

Glostrup Municipality, DK-2600, Denmark

Location

Institut National de la Santé et de la Reserche Médicale (INSERM)

Créteil, 94010, France

Location

Martin-Luther-University (MLU) of Halle-Wittenberg

Halle, 06097, Germany

Location

Deprtment of Psychiatry, University of Heidelberg

Mannheim, J 5, D-68159, Germany

Location

Ludwig-Maximilians University München

München, 80336, Germany

Location

Technische Universität München (TUM)

München, 81675, Germany

Location

Sheba Medical Centre Department of Psychiatry

Tel Litwinsky, 52621, Israel

Location

Department of Psychiatry University of Naples

Naples, 80138, Italy

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Department of Adult Psychiatry, University of Medical Sciences

Poznan, 60-572, Poland

Location

Obregia Psychiatric Hospital

Bucharest, 7000, Romania

Location

Hospital Clinic i Provincial

Barcelona, 08036 Barcelona, Spain

Location

Servicio Madrileño de Salud (SERMAS)

Madrid, 28007, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040 Madrid, Spain

Location

Instituto de Investigación Hospital 12 de Octubre

Madrid, 28041 Madrid, Spain

Location

Universidad de Oviedo

Oviedo, 33011 Oviedo, Spain

Location

Clienia Schlössli AG, Privatklinik für Psychiatrie und Psychotherapie

Oetwil, CH-8618, Switzerland

Location

King's College London, Departments of Psychological Medicine, Psychiatry & Cognitive Neuroscience

London, SE5 8AF, United Kingdom

Location

West London Mental Health Trust

London, W12 0NN, United Kingdom

Location

University of Manchester

Manchester, M13 9PL, United Kingdom

Location

Related Publications (4)

• Nasib LG, Winter-van Rossum I, Zuithoff NPA, Boudewijns ZSRM, Leucht S, Kahn RS. Generalizability of the Results of Efficacy Trials in First-Episode Schizophrenia: Comparing Outcome and Study Discontinuation of Groups of Participants in the Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) Trial. J Clin Psychiatry. 2023 Mar 29;84(3):22m14531. doi: 10.4088/JCP.22m14531.

  PMID: 36988483 DERIVED

• 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.

  PMID: 33838518 DERIVED

• 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.

  PMID: 33536130 DERIVED

• 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.

  PMID: 30115598 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Psychosocial Intervention

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• René Kahn, MD, PhD

  University Medical Center Utrecht, the Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: October 20, 2010
• First Posted: November 25, 2010
• Study Start: May 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 15, 2018

Record last verified: 2018-05

Locations

AU (1); IT (1); RO (1); GB (3); PL (1); NL (1); CZ (2); IL (1); BE (1); DE (4); CH (1); DK (1); BU (1); ES (5); FR (1)