Monotherapy of an NMDA Enhancer for Schizophrenia
Primary Purpose
Schizophrenia
Status
Recruiting
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
NMDAE
Placebo Cap
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, NMDA, Oxidative stress
Eligibility Criteria
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
Sites / Locations
- Department of Psychiatry, China Medical University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
NMDAE
Placebo
Arm Description
An NMDA enhancer
Placebo
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
Clinical Global Impression
Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.
Global Assessment of Functioning
Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.
Hamilton Rating Scale for Depression
Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.
Quality of Life Scale
Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.
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)
Full Information
NCT ID
NCT04745143
First Posted
January 14, 2021
Last Updated
August 6, 2023
Sponsor
China Medical University Hospital
Collaborators
National Health Research Institutes, Taiwan
1. Study Identification
Unique Protocol Identification Number
NCT04745143
Brief Title
Monotherapy of an NMDA Enhancer for Schizophrenia
Official Title
Monotherapy of an NMDA Enhancer for Schizophrenia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
China Medical University Hospital
Collaborators
National Health Research Institutes, Taiwan
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, NMDA, Oxidative stress
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
NMDAE
Arm Type
Experimental
Arm Description
An NMDA enhancer
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
NMDAE
Intervention Description
Use of an NMDA enhancer for the treatment of schizophrenia
Intervention Type
Drug
Intervention Name(s)
Placebo Cap
Intervention Description
Use of placebo as a comparator
Primary Outcome Measure Information:
Title
Change of Positive and Negative Syndrome Scale (PANSS)
Description
Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.
Time Frame
week 0, 2, 4, 6
Title
Change of scales for the Assessment of Negative Symptoms (SANS) total score
Description
Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.
Time Frame
week 0, 2, 4, 6
Secondary Outcome Measure Information:
Title
Positive subscale, Negative subscales, and General Psychopathology subscale of Positive and Negative Syndrome Scale (PANSS)
Description
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.
Time Frame
week 0, 2, 4, 6
Title
Clinical Global Impression
Description
Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.
Time Frame
week 0, 2, 4, 6
Title
Global Assessment of Functioning
Description
Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.
Time Frame
week 0, 2, 4, 6
Title
Hamilton Rating Scale for Depression
Description
Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.
Time Frame
week 0, 2, 4, 6
Title
Quality of Life Scale
Description
Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.
Time Frame
week 0, 2, 4, 6
Title
Cognitive function
Description
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)
Time Frame
Week 0, 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hsien-Yuan Lane, M.D., Ph.D
Phone
886 4 22052121
Ext
1855
Email
hylane@gmail.com
Facility Information:
Facility Name
Department of Psychiatry, China Medical University Hospital
City
Taichung
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hsien-Yuan Lane, M.D., Ph.D
Phone
886 4 22052121
Ext
1855
Email
hylane@gmail.com
12. IPD Sharing Statement
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Monotherapy of an NMDA Enhancer for Schizophrenia
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