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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01248195




Registration number
NCT01248195
Ethics application status
Date submitted
20/10/2010
Date registered
25/11/2010
Date last updated
15/05/2018

Titles & IDs
Public title
Optimization of Treatment and Management of Schizophrenia in Europe
Scientific title
Optimization of Treatment and Management of Schizophrenia in Europe
Secondary ID [1] 0 0
2010-020185-19
Secondary ID [2] 0 0
KP7242114
Universal Trial Number (UTN)
Trial acronym
OPTIMISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 0 0
Schizophreniform Disorder 0 0
Schizoaffective Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Schizophrenia
Mental Health 0 0 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Amisulpride open label
Treatment: Drugs - 6-week amisulpride double blind treatment
Treatment: Drugs - 6-week olanzapine double blind treatment
Treatment: Drugs - 12-week clozapine open-label treatment
Behaviour - Psychosocial intervention

Other: Phase I: 1 arm 'amisulpride open label' - For 4 weeks, all patients will be treated with amisulpride open label.

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'

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'

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'

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.

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.


Treatment: Drugs: Amisulpride open label
4-week open label amisulpride treatment

Treatment: Drugs: 6-week amisulpride double blind treatment
6-week amisulpride double blind treatment

Treatment: Drugs: 6-week olanzapine double blind treatment
6-week olanzapine double blind treatment

Treatment: Drugs: 12-week clozapine open-label treatment
12-week clozapine open-label treatment

Behaviour: Psychosocial intervention
Psychosocial intervention

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Behaviour
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Jan 2016
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Jan 2016
Primary outcome [3] 0 0
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).
Timepoint [3] 0 0
jan 2016
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
jan 2016
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
jan 2016
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
jan 2016
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
jan 2016
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
jan 2016
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
jan 2016
Secondary outcome [4] 0 0
MRI assessments - The ability of MRI to predict response to antipsychotic treatment in schizophrenia, after 4, 10 and 22 weeks.
Timepoint [4] 0 0
jan 2016

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Melbourne Neuropsychiatry Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3053 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Innsbruck
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Sofia
Country [4] 0 0
Czechia
State/province [4] 0 0
Ustavni 91
Country [5] 0 0
Czechia
State/province [5] 0 0
Hradec Králové
Country [6] 0 0
Denmark
State/province [6] 0 0
Glostrup
Country [7] 0 0
France
State/province [7] 0 0
Créteil Cedex
Country [8] 0 0
Germany
State/province [8] 0 0
Halle
Country [9] 0 0
Germany
State/province [9] 0 0
Mannheim
Country [10] 0 0
Germany
State/province [10] 0 0
München
Country [11] 0 0
Israel
State/province [11] 0 0
Tel Hashomer
Country [12] 0 0
Italy
State/province [12] 0 0
Naples
Country [13] 0 0
Netherlands
State/province [13] 0 0
Utrecht
Country [14] 0 0
Poland
State/province [14] 0 0
Poznan
Country [15] 0 0
Romania
State/province [15] 0 0
Bucuresti
Country [16] 0 0
Spain
State/province [16] 0 0
Barcelona
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid
Country [18] 0 0
Spain
State/province [18] 0 0
Oviedo
Country [19] 0 0
Switzerland
State/province [19] 0 0
Oetwil am See
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
Rene Kahn
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
King's College London
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Technische Universität München
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Manchester
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Ludwig-Maximilians - University of Munich
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01248195
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
René Kahn, MD, PhD
Address 0 0
University Medical Center Utrecht, the Netherlands
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications