Monotherapy of an NMDA Enhancer for Schizophrenia

March 21, 2026 updated by: China Medical University Hospital
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Hsien-Yuan Lane, M.D., Ph.D
  • Phone Number: 1855 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: 1855 886 4 22052121
          • Email: hylane@gmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 schizophrenia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of Positive and Negative Syndrome Scale (PANSS)
Time Frame: week 0, 2, 4, 6
Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.
week 0, 2, 4, 6
Change of scales for the Assessment of Negative Symptoms (SANS) total score
Time Frame: week 0, 2, 4, 6
Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.
week 0, 2, 4, 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive subscale, Negative subscales, and General Psychopathology subscale of Positive and Negative Syndrome Scale (PANSS)
Time Frame: week 0, 2, 4, 6

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
Clinical Global Impression
Time Frame: week 0, 2, 4, 6
Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.
week 0, 2, 4, 6
Global Assessment of Functioning
Time Frame: week 0, 2, 4, 6
Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.
week 0, 2, 4, 6
Hamilton Rating Scale for Depression
Time Frame: week 0, 2, 4, 6
Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.
week 0, 2, 4, 6
Quality of Life Scale
Time Frame: week 0, 2, 4, 6
Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.
week 0, 2, 4, 6
Cognitive function
Time Frame: Week 0, 6

The measure is the composite from multiple measures.

Ten cognitive tests for assessment of 7 cognitive domains:

  1. speed of processing (assessed by 3 tests: Category Fluency, Trail Marking A, WAIS-III Digit Symbol-Coding);
  2. sustained attention (Continuous Performance Test);
  3. working memory: verbal (digit span) and nonverbal (spatial span);
  4. verbal learning and memory (WMS-III, word listing);
  5. visual learning and memory (WMS-III, visual reproduction);
  6. reasoning and problem solving (WISC-III, Maze);
  7. social cognition (the Mayer-Salovey-Caruso Emotional Intelligence Test [MSCEIT] Version 2)
Week 0, 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

China Medical University Hospital

Collaborators

National Health Research Institutes, Taiwan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2018

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

January 14, 2021

First Submitted That Met QC Criteria

February 8, 2021

First Posted (Actual)

February 9, 2021

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 21, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMUH105-REC1-050

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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