Combination of NMDA-enhancing and Antioxidant Treatments for Schizophrenia

October 18, 2023 updated by: China Medical University Hospital
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.

Study Overview

Status

Recruiting

Conditions

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

90

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

      • 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
  • 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

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
Experimental: NMDAE plus Antioxidant agent (AO)
An NMDA enhancer plus a drug with antioxidant property
Use of an NMDA enhancer plus a drug with antioxidant property for the treatment of schizophrenia.
Placebo Comparator: NMDAE plus Placebo
An NMDA enhancer plus Placebo
Use of an NMDA enhancer plus placebo as a comparator.

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, 9, 12
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of scales for the Assessment of Negative Symptoms (SANS) total score
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.
week 0, 2, 4, 6, 9, 12
Positive subscale of PANSS
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
week 0, 2, 4, 6, 9, 12
Negative subscale of PANSS
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
week 0, 2, 4, 6, 9, 12
General Psychopathology subscale of PANSS
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome.
week 0, 2, 4, 6, 9, 12
Clinical Global Impression
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.
week 0, 2, 4, 6, 9, 12
Global Assessment of Functioning
Time Frame: week 0, 2, 4, 6, 9, 12
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
Hamilton Rating Scale for Depression
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome
week 0, 2, 4, 6, 9, 12
Quality of Life Scale
Time Frame: week 0, 2, 4, 6, 9, 12
Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.
week 0, 2, 4, 6, 9, 12
Cognitive function
Time Frame: Week 0, 12

Ten tests for assessment of 7 cognitive domains:

  1. speed of processing (assessed by 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 (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

Collaborators and Investigators

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

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)

November 30, 2020

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

June 10, 2021

First Submitted That Met QC Criteria

June 30, 2021

First Posted (Actual)

July 13, 2021

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

Other Study ID Numbers

  • CMUH108-REC1-177

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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