Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia

Schizophrenia Clinical Trial

Official title:

Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05240976
• Other study ID #: CMUH109-REC3-043
• Status: Recruiting
• Phase: Phase 2
• Start date: February 23, 2022
• Est. completion date: March 2027

Study information

• Verified date: August 2023
• Source: China Medical University Hospital
• Contact: Hsien-Yuan Lane, M.D., Ph.D
• Phone: 886 4 22052121
• Email: hylane[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• NMDAE plus AIFA
Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia.
• NMDAE plus Placebo Cap
Use of an NMDA enhancer plus placebo as a comparator

Locations

Country	Name	City	State
Taiwan	Department of Psychiatry, China Medical University Hospital	Taichung

Sponsors (2)

Lead Sponsor	Collaborator
China Medical University Hospital	National Health Research Institutes, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: speed of processing (assessed by Category Fluency, Trail Marking A, WAIS-III Digit Symbol-Coding); sustained attention (Continuous Performance Test); working memory: verbal (digit span) and nonverbal (spatial span); verbal learning and memory (WMS-III, word listing); visual learning and memory (WMS-III, visual reproduction); reasoning and problem solving (WISC-III, Maze); social cognition (MSCEIT Version 2)	Week 0, 12
Secondary	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).	week 0, 2, 4, 6, 9, 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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