Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change of cognitive function
研究概览
简要总结
Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.
详细描述
Several lines of evidence suggest that both NMDA and inflammatory hypotheses have been implicated in schizophrenia. Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.
Therefore, this study aims to compare NMDAE plus a drug with anti-inflammatory property and NMDAE plus placebo in the treatment of ultra-resistant schizophrenia. The subjects are the patients with ultra-resistant schizophrenia who have responded poorly to clozapine treatment. They keep their original clozapine treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE plus Anti-inflammatory Agent (AIFA), or (2) NMDAE plus placebo. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. The efficacies of NMDAE plus AIFA and NMDAE plus placebo will be compared.
Chi-square (or Fisher's exact test) will be used to compare differences of categorical variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous variables between treatment groups. Mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE) for both primary and secondary outcomes . All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
- •Are treatment-resistant to standard treatments of at least two specific antipsychotics before clozapine treatment
- •Are receiving adequate trials of clozapine for more than 12 weeks but without satisfactory response
- •PANSS total score ≥ 70; SANS total score ≥ 40
- •Have sufficient education to communicate effectively and are capable of completing the assessments of the study
- •Agree to participate in the study and provide informed consent
排除标准
- •DSM-5 diagnosis of intellectual disability or substance (including alcohol) use disorder
- •History of epilepsy, head trauma, or serious medical or central nervous system diseases (other than schizophrenia) which may interfere with the study
- •Clinically significant laboratory screening tests (including blood routine, biochemical tests)
- •Pregnancy or lactation
- •Inability to follow protocol
研究组 & 干预措施
NMDAE plus Anti-inflammatory Agent (AIFA)
An NMDA enhancer plus a drug with anti-inflammatory property
干预措施: NMDAE plus AIFA (Drug)
NMDAE plus Placebo
An NMDA enhancer plus Placebo
干预措施: NMDAE plus Placebo Cap (Drug)
结局指标
主要结局
Change of cognitive function
时间窗: Week 0, 12
The measure is the composite from multiple measures. All tests have no unit. For the domain (a. and c.) with more than one test, a composite T score will be calculated by standardizing the average of each T score. Furthermore, a global composite score (for all seven domains) and a neurocognitive composite score (for the first 6 domains) will be also calculated by standardizing the average of the T score of each domain (Lane HY et al, JAMA Psychiatry 2013). Ten tests for assessing 7 cognitive domains: 1. speed of processing (assessed by Category Fluency, Trail Marking A, WAIS-III Digit Symbol-Coding); 2. sustained attention (Continuous Performance Test); 3. working memory: verbal (digit span) and nonverbal (spatial span); 4. verbal learning and memory (WMS-III, word listing); 5. visual learning and memory (WMS-III, visual reproduction); 6. reasoning and problem solving (WISC-III, Maze); 7. social cognition (MSCEIT Version 2)
次要结局
- Change of Positive and Negative Syndrome Scale (PANSS)(week 0, 2, 4, 6, 9, 12)
- Change of scale for the Assessment of Negative Symptoms (SANS) total score(week 0, 2, 4, 6, 9, 12)
- Change of negative subscale of PANSS(week 0, 2, 4, 6, 9, 12)
- Change of general Psychopathology subscale of PANSS(week 0, 2, 4, 6, 9, 12)
- Change of clinical Global Impression(week 0, 2, 4, 6, 9, 12)
- Change of hamilton Rating Scale for Depression(week 0, 2, 4, 6, 9, 12)
- Change of quality of Life Scale(week 0, 2, 4, 6, 9, 12)
- Chang of positive subscale of PANSS(week 0, 2, 4, 6, 9, 12)
- Change of global Assessment of Functioning(week 0, 2, 4, 6, 9, 12)