Clinical trial NCT05240976: Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia
Official title: Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Ultra-resistant schizophrenia
NMDA
Inflammation
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: National Health Research Institutes, Taiwan
First posted: 2022-02-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Change of cognitive function
timeFrame: Week 0, 12
Secondary outcomes:
measure: Change of Positive and Negative Syndrome Scale (PANSS)
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of scale for the Assessment of Negative Symptoms (SANS) total score
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Chang of positive subscale of PANSS
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of negative subscale of PANSS
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of general Psychopathology subscale of PANSS
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of clinical Global Impression
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of global Assessment of Functioning
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of hamilton Rating Scale for Depression
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Change of quality of Life Scale
timeFrame: week 0, 2, 4, 6, 9, 12
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: