Monotherapy of an NMDA Enhancer for Schizophrenia

Schizophrenia Clinical Trial

Official title:

Monotherapy of an NMDA Enhancer for Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04745143
• Other study ID #: CMUH105-REC1-050
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2018
• Est. completion date: December 2025

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 studies found that some NMDA-enhancing agent was able to augment antioxidant activity and its adjunctive therapy was better than placebo in reducing clinical symptoms and cognitive deficits and revealed favorable safety in patients with chronic schizophrenia. Of note, a substantial portion of schizophrenia patients refuse or cannot tolerate antipsychotics due to poor response or severe side effects. Therefore, this study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) as a monotherapy for the treatment of schizophrenia.

Description:

Several lines of evidence suggest that schizophrenia is associated with accelerated aging and oxidative stress may play a role. Cognitive deficits are core symptoms of accelerated aging in patients with schizophrenia and the most difficult domain to treat. Current antipsychotics have limited, if any, efficacy for cognitive function. Previous studies found that some NMDA-enhancing agent was able to augment antioxidant activity and its adjunctive therapy was better than placebo in reducing not only clinical symptoms but also cognitive deficits and revealed favorable safety in patients with chronic schizophrenia. Of note, a substantial portion of schizophrenia patients refuse or cannot tolerate antipsychotics due to poor response or severe side effects. This study aims to examine the efficacy and safety of NMDAE monotherapy for the treatment of schizophrenia. The investigators enroll patients with schizophrenia who refuse or are unable to tolerate antipsychotics due to poor response or adverse effects into a 6-week randomized, double-blind trial to receive monotherapy of NMDAE or placebo. The investigators biweekly measure clinical performances and side effects. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of NMDAE and 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). 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: December 2025
• Est. primary completion date: September 2025
• 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

• Refuse or are unable to tolerate antipsychotics due to poor response or adverse effects

• PANSS total score = 60

• Free of antipsychotic drugs for at least 1 week

• Agree to participate in the study and provide informed consent

Exclusion Criteria:

• Current substance abuse or history of substance dependence in the past 3 months

• History of epilepsy, head trauma, stroke or other serious medical or neurological illness which may interfere with the study

• Use of depot antipsychotic in the past 3 months;

• Clinically significant laboratory screening tests

• Pregnancy or lactation

• Inability to follow protocol

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• NMDAE
Use of an NMDA enhancer for the treatment of schizophrenia
• Placebo Cap
Use of 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 Positive and Negative Syndrome Scale (PANSS)	Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.	week 0, 2, 4, 6
Primary	Change of scales 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
Secondary	Positive subscale, Negative subscales, and General Psychopathology subscale of Positive and Negative Syndrome Scale (PANSS)	PANSS-positive: Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.; PANSS-negative: Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.; PANSS-general psychopathology: Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome.	week 0, 2, 4, 6
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cognitive function	The measure is the composite from multiple measures.; Ten cognitive tests for assessment of 7 cognitive domains: speed of processing (assessed by 3 tests: 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 (the Mayer-Salovey-Caruso Emotional Intelligence Test [MSCEIT] Version 2)	Week 0, 6