A Randomized Controlled Trial With Rituximab for Psychotic Disorder in Adults
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 123
- 试验地点
- 2
- 主要终点
- Proportion of responders to treatment, rated as much or very much improved with CGI-I
研究概览
简要总结
Immunological factors are assumed to be determinants for some psychiatric disorders, thus anti-inflammatory drugs may be helpful. However, studies on such treatments are scarce. An inflammatory modulating drug rituximab, cluster of differentiation antigen 20 antibodies (anti-CD20 antibodies), is a standard treatment for e.g. multiple sclerosis.
The investigators aim to test rituximab in a randomised placebo-controlled double-blinded, add-on treatment trial in 120 participants (18-55 years) with schizophrenia spectrum disorder. Sampling from blood for analyses of inflammatory mediators are investigated at gene and protein levels and resting state functional magnetic resonance imaging (rsfMRI) and lumbar puncture are optional. Biomarkers will be investigated in relation to treatment response.
Family member(s) to the patient and the patient (separate) will be asked to participate in a qualitative interview by an independent researcher after 3 months.
详细描述
Immunological factors are assumed to be determinants for some psychiatric disorders, thus anti-inflammatory drugs may be helpful. However, studies on such treatments are scarce. Rituximab (anti-CD20 antibodies), a standard treatment for multiple sclerosis in Sweden, is an inflammatory modulating drug. In a small open pilot trial, markedly ill, treatment-resistant participants with schizophrenia spectrum disorder were treated with a single- dose rituximab (1000 mg), as add-on treatment to antipsychotics in Örebro, Sweden (2019-2022). Large improvements in all types of psychotic symptoms were evident, with long-lasting effects and few side-effects in most of the participants.
This is a proof-of-concept study based on our earlier findings. The investigators will conduct a multicenter, placebo-controlled, double-blinded, add-on intervention study for 120 participants with schizophrenia spectrum disorder (18-55 years). Sampling from blood for analyses of inflammatory mediators are investigated at gene and protein levels and rsfMRI and lumbar puncture are optional at baseline and endpoints. Biomarkers will be investigated in relation to treatment response.
Participants are assessed at five time-points; week 0, 2, 7, 12 (endpoint I) and 24 (endpoint II).
Research questions:
I Does the addition of rituximab to standard psychiatric treatment improve psychotic symptoms in SSD?
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)
盲法说明
informant, psychologist, laboratory staff
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ages 18 to 55 years
- •duration of illness exceeding 1 year
- •diagnosed with Schizophrenia spectrum disorder (SSD) according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
- •if female and with any risk for pregnancy, willing to use contraceptives or abstinence if normal and preferred lifestyle.
- •participants should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent.
- •insufficiently recovered from previous antipsychotic treatments.
- •a minimum score of 4 (moderately ill) in Clinical global impression - severity (CGI-S) at baseline.
排除标准
- •pregnancy or breast-feeding
- •weight below 40 kg
- •clinically relevant ongoing infection at the discretion of the physician
- •chronic infections
- •positive test for hepatitis B, hepatitis C, HIV, or tuberculosis
- •malignancy currently or within 2 years prior to inclusion
- •current severe heart failure (NYHA grade IV) or any other severe heart disease (e.g. or history of cardiac arrhythmia or myocardial infarction)
- •any change of antipsychotic medication within the previous 4 weeks
- •unable to make an informed decision to consent to the trial
- •ongoing clozapine treatment
- •ongoing immunomodulatory treatment
- •treatments with monoclonal antibodies within 1 year before the inclusion
研究组 & 干预措施
Rituximab
Rituximab 1000 mg, infusion
干预措施: Rituximab (Drug)
Placebo
Saline infusion
干预措施: Rituximab (Drug)
结局指标
主要结局
Proportion of responders to treatment, rated as much or very much improved with CGI-I
时间窗: Baseline up to week 12
Improvement according to clinical rated Clinical Global Impression-Improvement (CGI-I)
次要结局
- Improvement in functioning(Baseline up to week 12 and 24)
- Change in psychotic symptoms(Baseline up to 12 weeks)
- Proportion of responders to treatment, rated as much or very much improved with CGI-I(Baseline up to week 24)
- Improvement since baseline(Baseline up to week 12 and 24)
- Change in severity since baseline(Baseline up to week 12 and 24)
- Improvement in psychotic symptoms since baseline(Baseline up to week 24)
- Change in self-rated overall health(Baseline up to week 12 and 24)
- Patient-rated improvement(Baseline up to week 12 and 24)
- Safety and tolerability of rituximab(Baseline up to week 12 and 24)
- fMRI(Baseline up to week 12 and 24)
- Patient-rated change in psychiatric symptoms(Baseline up to week 12 and 24)
- Inflammatory markers in blood and/or cerebro spinal fluid (CSF)(Baseline up to week 12 and 24)
- Change in PANSS separate subscales and Marder negative factor.(Week 12 and week 24.)