Combination of NMDA-enhancing and Antioxidant Treatments for Schizophrenia

Schizophrenia Clinical Trial

Official title:

Combination of NMDA-enhancing and Antioxidant Treatments for Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04959201
• Other study ID #: CMUH108-REC1-177
• Status: Recruiting
• Phase: Phase 2
• Start date: November 30, 2020
• Est. completion date: March 2025

Study information

• Verified date: October 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 agents were able to improve clinical symptoms of patients with schizophrenia. In addition, several drugs with antioxidant properties have been tested in clinical trials for the treatment of schizophrenia too. Whether combined treatment of an NMDA-enhancing agent and a drug with antioxidant property can be better than an NMDA-enhancing agent alone deserves study.

Description:

Several lines of evidence suggest that both NMDA and oxidative stress hypotheses have been implicated in schizophrenia. Previous studies found that some NMDA-enhancing agents were able to augment efficacy of antipsychotics in the treatment of schizophrenia. In addition, several drugs with antioxidant properties have been tested in clinical trials for the treatment of schizophrenia too. Whether a drug with antioxidant property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of schizophrenia remains unknown. Therefore, this study aims to compare NMDAE plus a drug with antioxidant property and NMDAE plus placebo in the treatment of schizophrenia. The subjects are the schizophrenia patients who remain symptomatic while having been stabilized with antipsychotic treatment. They keep their original treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE plus Antioxidant agent (AO), or (2) NMDAE plus placebo. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of NMDAE plus AO 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). 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: 90
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• 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
• Remain symptomatic but without clinically significant fluctuation, while their antipsychotic doses are unchanged for at least 3 months and will be maintained during the period of the 12-week trial
• PANSS total score = 60
• 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, stroke, 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 AO
Use of an NMDA enhancer plus a drug with antioxidant property for the treatment of 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	Ministry of Science and Technology, 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, 9, 12
Secondary	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, 9, 12
Secondary	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	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	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	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	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	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	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
Secondary	Cognitive function	Ten tests for assessment of 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); All tests have no unit. Firstly, 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 (with a mean of 50 and a SD of 10 for making every test comparative). Secondly, a global composite score (for all seven domains) and a neurocognitive composite score (for the first 6 domains, a-f) will be also calculated by standardizing the average of the T score of each domain (Lane HY et al, JAMA Psychiatry. 2013).	Week 0, 12