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

Rene Kahn

Status and phase: Completed; Phase 4

Conditions: Schizophreniform Disorder; Schizophrenia; Schizoaffective Disorder

Treatments: Drug: 12-week clozapine open-label treatment; Behavioral: Psychosocial intervention; Drug: 6-week amisulpride double blind treatment; Drug: 6-week olanzapine double blind treatment; Drug: Amisulpride open label

Study type: Interventional

Funder types: Other

Identifiers

NCT01248195

2010-020185-19 (EudraCT Number)

KP7242114

Details and patient eligibility

About

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.

Full 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.

Enrollment: 479 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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479 participants in 6 patient groups

Phase I: 1 arm 'amisulpride open label'

Other group

Description:

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

Treatment:

Drug: Amisulpride open label

Phase II: 'amisulpride double blind'

Active Comparator group

Description:

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'

Treatment:

Drug: 6-week amisulpride double blind treatment

Phase II 'olanzapine double blind'

Active Comparator group

Description:

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'

Treatment:

Drug: 6-week olanzapine double blind treatment

Phase III: 1 arm 'clozapine open label'

Other group

Description:

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'

Treatment:

Drug: 12-week clozapine open-label treatment

Psychosocial intervention

Experimental group

Description:

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.

Treatment:

Behavioral: Psychosocial intervention

Psychosocial Intervention phase: 'TAU'

No Intervention group

Description:

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.