Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by UMC Utrecht
Sponsor:
Collaborators:
King's College London
Technische Universität München
University of Manchester
Ludwig-Maximilians - University of Munich
Information provided by (Responsible Party):
Rene Kahn, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01248195
First received: October 20, 2010
Last updated: July 16, 2015
Last verified: July 2015
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimization of Treatment and Management of Schizophrenia in Europe

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • PANSS [ Time Frame: Jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    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 [ Time Frame: jan 2016 ] [ Designated as safety issue: No ]
    The ability of MRI to predict response to antipsychotic treatment in schizophrenia, after 4, 10 and 22 weeks.


Estimated Enrollment: 500
Study Start Date: May 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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.

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

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01248195

  Show 26 Study Locations
Sponsors and Collaborators
Rene Kahn
King's College London
Technische Universität München
University of Manchester
Ludwig-Maximilians - University of Munich
Investigators
Principal Investigator: René Kahn, MD, PhD University Medical Center Utrecht, the Netherlands
  More Information

Additional Information:
No publications provided

Responsible Party: Rene Kahn, MD PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01248195     History of Changes
Other Study ID Numbers: KP7242114, 2010-020185-19
Study First Received: October 20, 2010
Last Updated: July 16, 2015
Health Authority: Austria: Ethikkommission
Belgium: Federal Agency for Medicinal Products and Health Products
Bulgaria: Ethics committee
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ethics Commission
Israel: Ethics Commission
Italy: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Romania: National Agency for Medicines and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Human Research Ethics Committee

Keywords provided by UMC Utrecht:
Schizophrenia
Schizophreniform disorder
Schizoaffective disorder
Imaging
Prognosis
Treatment guidelines
Pharmacogenetics

Additional relevant MeSH terms:
Disease
Psychotic Disorders
Schizophrenia
Mental Disorders
Pathologic Processes
Schizophrenia and Disorders with Psychotic Features
Clozapine
Olanzapine
Sulpiride
Sultopride
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
GABA Agents
GABA Antagonists
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents

ClinicalTrials.gov processed this record on July 30, 2015