Optimization of Treatment and Management of Schizophrenia in Europe
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 479
- 试验地点
- 26
- 主要终点
- Sellwood rating scale
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Phase I: 1 arm 'amisulpride open label'
For 4 weeks, all patients will be treated with amisulpride open label.
干预措施: Amisulpride open label (Drug)
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'
干预措施: 6-week amisulpride double blind treatment (Drug)
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'
干预措施: 6-week olanzapine double blind treatment (Drug)
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'
干预措施: 12-week clozapine open-label treatment (Drug)
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.
干预措施: Psychosocial intervention (Behavioral)
结局指标
主要结局
Sellwood rating scale
时间窗: 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.
MRS measures
时间窗: 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.
Biological profile
时间窗: 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).
PANSS
时间窗: 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.
SOFAS global functioning
时间窗: 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
时间窗: 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.
次要结局
- Biological markers(jan 2016)
- MRI assessments(jan 2016)
- All cause treatment discontinuation(jan 2016)
- All cause discontinuation(jan 2016)
研究者
Rene Kahn
MD PhD
UMC Utrecht