SchizophreniaPhase 2NCT04959201
Combination of NMDA-enhancing and Antioxidant Treatments for Schizophrenia
A Phase 2 study testing NMDAE plus AO in people with Schizophrenia, run by China Medical University Hospital at 1 site in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- NMDAE plus AO
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteTaiwan
- Study dates
- 30 Nov 2020to Mar 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
Department of Psychiatry, China Medical University Hospital
Taichung
Hsien-Yuan Lane, M.D., Ph.D, 886 4 22052121 ext. 1855, hylane@gmail.com
About this study
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- NMDAE plus AO, NMDAE plus Placebo Cap
- Keywords
- Schizophrenia, NMDA, Oxidative stress
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMDAE plus AODrug
Use of an NMDA enhancer plus a drug with antioxidant property for the treatment of schizophrenia.
NMDAE plus Placebo CapDrug
Use of an NMDA enhancer plus placebo as a comparator.
| Study group | Role | What they receive |
|---|---|---|
| NMDAE plus Antioxidant agent (AO) | Experimental | An NMDA enhancer plus a drug with antioxidant property Receives: Drug: NMDAE plus AO |
| NMDAE plus Placebo | Placebo comparator | An NMDA enhancer plus Placebo Receives: Drug: NMDAE plus Placebo Cap |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: week 0, 2, 4, 6, 9, 12
Secondary outcomes (9)
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.
Measured: week 0, 2, 4, 6, 9, 12
Positive subscale of PANSS
Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
Measured: week 0, 2, 4, 6, 9, 12
Negative subscale of PANSS
Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
Measured: week 0, 2, 4, 6, 9, 12
General Psychopathology subscale of PANSS
Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome.
Measured: week 0, 2, 4, 6, 9, 12
Clinical Global Impression
Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.
Measured: week 0, 2, 4, 6, 9, 12
Global Assessment of Functioning
Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.
Measured: week 0, 2, 4, 6, 9, 12
Hamilton Rating Scale for Depression
Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome
Measured: week 0, 2, 4, 6, 9, 12
Quality of Life Scale
Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.
Measured: week 0, 2, 4, 6, 9, 12
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).
Measured: Week 0, 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2021
- Study start30 Nov 2020
- Primary completionDec 2026 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04959201
- Sponsor's protocol ID
- CMUH108-REC1-177
- Status last verified
- Oct 2026
- First submitted
- 10 Jun 2021
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No