Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: NMDAE plus AIFA, NMDAE plus Placebo Cap.
- Who it may be relevant to
- Registry conditions: Schizophrenia. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Taiwan
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Detailed description
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.
Interventions
- Drug NMDAE plus AIFA
Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia. - Drug NMDAE plus Placebo Cap
Use of an NMDA enhancer plus placebo as a comparator
Primary outcome measures
- Change of cognitive function [Time frame: Week 0, 12]
Secondary outcome measures (9)
- Change of Positive and Negative Syndrome Scale (PANSS) [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of scale for the Assessment of Negative Symptoms (SANS) total score [Time frame: week 0, 2, 4, 6, 9, 12]
- Chang of positive subscale of PANSS [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of negative subscale of PANSS [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of general Psychopathology subscale of PANSS [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of clinical Global Impression [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of global Assessment of Functioning [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of hamilton Rating Scale for Depression [Time frame: week 0, 2, 4, 6, 9, 12]
- Change of quality of Life Scale [Time frame: week 0, 2, 4, 6, 9, 12]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Triple blind
- Primary purpose
- Treatment
Study locations
Taiwan · 1 center
- Department of Psychiatry, China Medical University Hospital — Taichung
Identifiers
NCT: NCT05240976 · CMUH109-REC3-043