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.
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
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
Parallel
NMDAE plus AIFA
DrugUse of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia.
NMDAE plus Placebo Cap
DrugUse of an NMDA enhancer plus placebo as a comparator
Change of cognitive function
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)
Change of Positive and Negative Syndrome Scale (PANSS)
Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome. As shown in "Detailed Description", "mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE) for both primary and secondary outcomes. That is, GEE is used for analyzing the changes from baseline in repeated-measure assessments by a single analysis (but not multiple analyses).
Change of scale for the Assessment of Negative Symptoms (SANS) total score
Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.
Chang of positive subscale of PANSS
Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
Change of negative subscale of PANSS
Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
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China Medical University Hospital
Lead sponsor
National Health Research Institutes, Taiwan
Collaborator
