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| Name | Class |
|---|---|
| National Health Research Institutes, Taiwan | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NMDAE plus Anti-inflammatory Agent (AIFA) | Experimental | An NMDA enhancer plus a drug with anti-inflammatory property |
|
| NMDAE plus Placebo | Placebo Comparator | An NMDA enhancer plus Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NMDAE plus AIFA | Drug | Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| Week 0, 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hsien-Yuan Lane, M.D., Ph.D | Contact | 886 4 22052121 | 1855 | hylane@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Psychiatry, China Medical University Hospital | Recruiting | Taichung | Taiwan |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| NMDAE plus Placebo Cap | Drug | Use of an NMDA enhancer plus placebo as a comparator |
|
| week 0, 2, 4, 6, 9, 12 |
| 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. | week 0, 2, 4, 6, 9, 12 |
| Chang of positive subscale of PANSS | Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome. | week 0, 2, 4, 6, 9, 12 |
| Change of negative subscale of PANSS | Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome. | week 0, 2, 4, 6, 9, 12 |
| Change of general Psychopathology subscale of PANSS | Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome | week 0, 2, 4, 6, 9, 12 |
| Change of clinical Global Impression | Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome. | week 0, 2, 4, 6, 9, 12 |
| Change of global Assessment of Functioning | Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function. | week 0, 2, 4, 6, 9, 12 |
| Change of hamilton Rating Scale for Depression | Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome. | week 0, 2, 4, 6, 9, 12 |
| Change of quality of Life Scale | Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome. | week 0, 2, 4, 6, 9, 12 |