Biomarkers in Clozapine-responding Schizophrenia
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Qalb
研究概览
简要总结
The outline of the current project is to establish a cohort of patients with treatment refractory schizophrenia eligible for clozapine, to identify clinical and biological characteristics of clozapine responding patients. Patients will be offered treatment with clozapine according to national clinical guidelines. Before clozapine is initiated, patients will be offered a thoroughly neurobiological examination, and re-examination will be carried out after 12 weeks of treatment. The primary focus of the examinations will be immunological markers and autoantibodies in the blood and cerebrospinal fluid, permeability of the blood-brain barrier and magnetic resonance imaging of structural, neurochemical and functional brain changes.
详细描述
Patients will be examined before and after 12 weeks of treatment with clozapine
Examinations at baseline and follow up will be:
- Clinical ratings
- Blood inflammatory markers
- Inflammatory markers in cerebro spinal fluid
- MRI : examination of grey & white matter, glutamate and GABA in Anterior Cingulate cortex and glutamate in thalamus,
- selected cognitive measures
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •According to ICD-10 fulfill diagnostic criteria for schizophrenia (F20.x), chronical paranoid psychoses (F22), Schizoaffective psychoses (F25) or other non-organic psychoses (F28/F29);
- •Age 18-65 years;
- •Legally competent;
- •Stabil antipsychotic treatment during last month
- •Being treatment refractory according to TRIPP-guidelines (Howes et al. 2017) defined as having tried at least two antipsychotic drugs in sufficient dosage (≥600 mg chlorpromazine equivalent) for a sufficient time (≥ 6 weeks) without sufficient symptom improvement (still a moderate level of positive symptoms).
- •Recreational use of substances is allowed as long as it does not interfere with compliance
- •Fertile females must use safe contraception (spiral or any hormonal contraception).
排除标准
- •Involuntarily psychiatric admittance during the study
- •Substance abuse that interfere with compliance
- •Pregnancy (will be verified by urine-HCG-test in fertile females)
- •Toxic or idiosyncratic agranulocytosis in the past
- •Reduced bone marrow function according to blood samples
- •According to information from patient and available files, noUncontrolled
- •Current uncontrolled epilepsy
- •Current circulatory collapse and / or CNS depression for any cause
- •Current severe kidney, heart or liver disease
- •Current paralytic ileus
研究组 & 干预措施
clozapine treatment
Open label clozapine will be given to all participants in clinical doses adjusted to sideeffects and clinical effect
干预措施: Clozapine (Drug)
结局指标
主要结局
Qalb
时间窗: Baseline
Quotient albumin (Qabl) in cerebrospinal fluid (CSF) compared to plasma
Change in Qalb
时间窗: Baseline and after 12 weeks
Change in quotient albumin in cerebrospinal fluid compared to plasma
Change in IL-6 and TGF-beta
时间窗: Baseline and after 12 weeks
Change in interleukin 6 (IL-6) and transcription growth factor beta (TGF-beta)
次要结局
- Change in FA, MD, AD and RD(Baseline and after 12 weeks)
- Change in cortical thickness as measured with FreeSurfer(Baseline and after 12 weeks)
- Change in glutamate in ACC and thalamus measured with MTI(Baseline and after 12 weeks)
研究者
Jimmi Nielsen
Professor
Copenhagen University Hospital, Hvidovre