NMDA-enhancing Treatment for Cognitive Dysfunction of Schizophrenia

NMDA-enhancing Treatment for Cognitive Dysfunction of Schizophrenia Patients During Symptomatic Remission

Cognitive impairment, the core psychopathology of schizophrenia, usually persists in schizophrenia patients even during symptomatic remission. While cognitive impairment associated with schizophrenia (CIAS) is an important therapeutic target, hypofunction of N-methyl-D-aspartate receptor (NMDAR) is a key factor of CIAS. This study aims to examine the efficacy and safety of an NMDA-enhancer (NMDAE) for the treatment of CIAS in schizophrenia patients during symptomatic remission.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo Cap; Drug: NMDAE

Detailed Description

Cognitive impairment, the core psychopathology and the outcome determinant of schizophrenia, usually persists in schizophrenia patients even during symptomatic remission. Cognitive impairment associated with schizophrenia (CIAS) is an important therapeutic target; and hypofunction of N-methyl-D-aspartate receptor (NMDAR) is a key factor of CIAS. Whether NMDAR-enhancing treatment can truly improve cognitive function needs to be tested in schizophrenia patients during symptomatic remission. This study aims to examine the efficacy and safety of an NMDA-enhancer (NMDAE) for the treatment of CIAS in schizophrenia patients during symptomatic remission.

The subjects are the patients with schizophrenia during symptomatic remission. They keep their original treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE, or (2) placebo. At weeks 0 and 12, 7 cognitive domains will be measured. At weeks 0, 4, 8, and 12, Global Assessment of Function, Quality of Life Scale, various clinical-symptom rating scales, and side effects scales will be measured too.

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hsien-Yuan Lane, M.D., Ph.D; Phone Number: 11855 886 4 22052121; Email: hylane@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Recruiting
    • Department of Psychiatry, China Medical University Hospital
    • Contact: Hsien-Yuan Lane, M.D., Ph.D; Phone Number: 11855 886 4 22052121; Email: hylane@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5 -TR) diagnosis of schizophrenia
• Fulfill the Remission in Schizophrenia Working Group (RSWG) criteria for remission (Andreasen et al., 2005): each of eight items (delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, passive/apathetic social withdrawal, and lack of spontaneity and flow of conversation) in the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987) scoring 3 or lower for 6 months or longer; in addition, have a baseline total score of 59 or lower in the PANSS
• Are physically healthy and laboratory assessments (including blood routine, biochemical tests) are clinically insignificant;
• Have been keeping a fixed dose of antipsychotics (excluding clozapine) for at least 6 months, and that is not allowed to change during the 12-week study period
• Have sufficient education to communicate effectively and are capable of completing the assessments of the study
• Agree to participate in the study and provide written informed consent

Exclusion Criteria:

• DSM-5-TR 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
• Pregnancy or lactation
• Inability to follow protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Cap; Use of placebo as a comparator
Experimental: NMDAE; An NMDA enhancer	Drug: NMDAE; Use of an NMDA enhancer for the treatment of CIAS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of cognitive function composite	Ten tests for assessment of 7 cognitive domains: speed of processing (assessed by Category Fluency, Trail Marking A, Wechsler Adult Intelligence Scale(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) 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 (Lane HY et al, JAMA Psychiatry 2013)	Week 0, 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Global Assessment of Functioning composite	Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.	week 0, 4, 8, 12
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, 4, 8, 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, 4, 8, 12
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, 4, 8, 12
Change of Positive subscale of PANSS	Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.	week 0, 4, 8, 12
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, 4, 8, 12
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, 4, 8, 12
Change of Clinical Global Impression	Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.	week 0, 4, 8, 12
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, 4, 8, 12

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: National Science and Technology Council, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: August 28, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia; NMDA; Symptomatic remission
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Schizophrenia; Cognitive Dysfunction
• Other Study ID Numbers: CMUH111-REC3-228

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No