Functional Connectivity and Associated Neuropeptides Variations in Treatment Resistant Schizophrenia Patients: Treatment Efficacy of add-on Sodium Benzoate
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Brain imaging, functional MRI
研究概览
简要总结
Although antipsychotic is effective for schizophrenia, however, still certain proportion of patients were not responsive to treatment. Treatment resistant schizophrenia (TRS) is accompanied by function decline and heavy burden. In recent decades, the biological mechanism of schizophrenia extended from dopamine theory to the role of glutamate system. This shift could be an alternative pathway to developing the treatment of TRS. Sodium benzoate (SB) could be an option as a glutamatergic agent for the patients with TRS. However, most evidence of SB is for treating patients with schizophrenia and other mental disorders but the evidence for treating patients with TRS is scarce. To predict the treatment response of SB will be an urgent topic in the future. Little is known about the precise medicine for treating patients with TRS. The present project will extend our pilot randomized clinical trial on SB for TRS. A total of 90 patients with TRS will be enrolled from three centers and will be assigned to 8 weeks of treatment with SB or placebo (2:1). A comprehensive battery of potential markers will be employed, including 1H- magnetic resonance spectroscopy (MRS), brain functional connectivity, genotyping, immune biomarkers, cognitive function, and clinical characteristics. The efficacy of SB on TRS will be confirmed in this project. Predictors for treatment response will be identified. Artificial intelligence algorithms will be used for probing the feasibility of precision medicine.
详细描述
The design and instrument are identical for two years. This add-on sodium benzoate randomized, double-blinded, placebo-controlled trial which is a two-arm, 6-week follow-up trial. The 90 patients will be 2:1 (SB: placebo) randomly assigned to 1. Treatment with sodium benzoate (A); or 2. placebo (P). The group of sodium benzoate treatment will be divided into two subgroups: 1. Responder (AR), and nonresponder (AN), as illustrated in Figure 4. The response criteria is defined the improvement of 20% total PANSS score after 6-week SB treatment. The participants with TRS will be enrolled in this trail from 3 hospitals(National Cheng Kung University Hospital, Tainan Hospital, Ministry of Health and Welfare, Chia-Yi branch, Taichung Veteran General Hospital).
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
- 20 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfil the DSM5 criteria for schizophrenia or schizoaffective disorder
- •Research criteria for treatment resistance: little or no symptomatic response to multiple (at least two) antipsychotic treatment of an adequate duration (at least 6 weeks) and adequate doses (equivalent to at least 600 milliequivalent (meq)/day of chlorpromazine)
- •6 month period without remission (i.e. ≥4 item-score for the positive symptoms on PANSS scale , especially delusional thoughts, conceptual disorganisation, excitements, grandiosity, hallucinatory behaviour, excitement, persecution, and hostility)
- •The persistence of illness was defined as a score of ≥4 (moderately ill) on the severity of illness subscale of the Clinical Global Impression scale (CGI-S), and a lack of stable period of good social occupational function.
排除标准
- •Current or previous diagnosis of concurrent DSM-5 disorder due to active medical problems, known neurological disease, or a contraindication to MRI scanning
- •Current diagnosis of substance-related disorder
- •Any acute or chronic medical condition
- •History of head trauma or neurological diseases.
研究组 & 干预措施
Treatment resistant schizophrenia patients with augmentation of sodium benzoate 2g/day
with sodium benzoate 2g/day
干预措施: Sodium Benzoate 2gram/day (Drug)
Treatment resistant schizophrenia patients with augmentation of placebo
with placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Brain imaging, functional MRI
时间窗: 1hours
All participants were scanned using a 1.5 Tesla GE scanner with eight channel head coils. 1H-MRS was performed to assess the concentrations of excitatory, glutamine, glutamate, glutamate complex (Glx), GABA and other neurometabolites. A three-dimensional T1-weighted inversion recovery magnetic resonance imaging (MRI) scan was performed in all participants, axial MRI three-dimensional brain volume, echo time (TE) = 2.9 ms, repetition time (TR) = 7.7, inversion time = 450 ms, flip angle = 12°, field of view =230 mm, matrix size = 256 × 256, and slice thickness = 1.0 mm
次要结局
- Wechsler adult intelligence scales 4th edition (WAIS-IV)(1 hours)
- Clinical psychiatric condition, Positive and Negative Symptoms Scale (PANSS)(20 minutes)
- Wisconsin card sorting test (WCST)(20 minutes)
- Continuous performance test third edition (CPT-3)(20 minutes)