SchizophreniaPhase 2NCT06574360
Dual Modulation of Sigma-1 and NMDA Receptors in the Treatment of Schizophrenia
A Phase 2 study testing S1RA plus NMDAE in people with Schizophrenia, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
sigma-1 receptor (S1R) agonistic property have been tested in clinical trials for the treatment of schizophrenia. In addition, previous studies found that some NMDA receptor (NMDAR)-enhancing agents were able to improve clinical symptoms of patients with chronic schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- S1RA plus NMDAE
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteTaiwan
- Study dates
- 23 Sep 2024to Mar 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Are resistant to adequate treatments of at least two antipsychotics (excluding clozapine)
- 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 8-week trial
- PANSS total score >70
- Hamilton Depression Rating Scale-17 items (HAMD) <7
- Are physically healthy and laboratory assessments (including blood routine, biochemical tests) are clinically insignificant.
- Have sufficient education to communicate effectively and are capable of completing the assessments of the study.
- 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, central nervous system diseases or mental disorders other than schizophrenia (including major depressive disorder, bipolar disorders, persistent depressive disorder, obsessive-compulsive disorder)
- 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
sigma-1 receptor (S1R) agonistic property have been tested in clinical trials for the treatment of schizophrenia. In addition, previous studies found that some NMDA receptor (NMDAR)-enhancing agents were able to improve clinical symptoms of patients with chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancing agent can be better than an S1R agonist alone deserves study.
Read the detailed description
The current treatment for schizophrenia remains unsatisfactory; thus, development of new treatments is vital. Both sigma-1 receptor (S1R) dysfunction and NMDA receptor (NMDAR) hypofunction contribute to pathogenesis of schizophrenia, especially treatment-resistant schizophrenia. Several S1R agonists have been tested for its potential for schizophrenia treatment; however, its efficacy appears limited. In addition, previous studies also found that some NMDA-enhancing agents were able to augment efficacy of antipsychotics in the treatment of chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancer (NMDAE) can be better than an S1R agonist alone deserves study. Therefore, this study aims to compare an S1R agonist plus an NMDAE and an S1R agonist plus placebo in the treatment of treatment-resistant schizophrenia. The subjects are the patients with treatment-resistant schizophrenia who have responded poorly to two or more kinds of antipsychotics treatment. They keep their original treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) S1R agonist (S1RA) plus NMDAE, or (2) S1RA plus placebo. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, and 8. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of S1RA plus NMDAE and S1RA 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
- S1RA plus NMDAE, S1RA plus Placebo Cap
- Keywords
- Schizophrenia, NMDA, sigma-1 receptor
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S1RA plus NMDAEDrug
Use of an S1R agonist plus an NMDA enhancer for the treatment of treatment-resistant schizophrenia.
S1RA plus Placebo CapDrug
Use of an S1R agonist plus placebo as a comparator
| Study group | Role | What they receive |
|---|---|---|
| S1R agonist (S1RA) plus NMDAE | Experimental | An S1R agonist plus an NMDA enhancer Receives: Drug: S1RA plus NMDAE |
| S1R agonist (S1RA) plus placebo | Placebo comparator | An S1R agonist plus placebo Receives: Drug: S1RA 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, 8
Secondary outcomes (6)
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, 8
Positive subscale, Negative subscales, and General Psychopathology subscale of 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.
Measured: week 0, 2, 4, 6, 8
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, 8
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, 8
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, 8
Cognitive function
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)
Measured: Week 0, 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2024
- Study start23 Sep 2024
- Primary completionDec 2028 (estimated)
- Study completionMar 2029 (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.
- More trials run by China Medical University HospitalThe sponsor's other registered studies.
- 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
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06574360
- Sponsor's protocol ID
- CMUH112-REC3-202
- Status last verified
- Mar 2026
- First submitted
- 25 Aug 2024
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual Modulation of Sigma-1 and NMDA Receptors in the Treatment of Schizophrenia
- ClinicalTrials.gov ID
- NCT06574360
- Acronym / sponsor ID
- CMUH112-REC3-202
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, NMDA, sigma-1 receptor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- 23 Sep 2024 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 27 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
sigma-1 receptor (S1R) agonistic property have been tested in clinical trials for the treatment of schizophrenia. In addition, previous studies found that some NMDA receptor (NMDAR)-enhancing agents were able to improve clinical symptoms of patients with chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancing agent can be better than an S1R agonist alone deserves study.
Detailed description
The current treatment for schizophrenia remains unsatisfactory; thus, development of new treatments is vital. Both sigma-1 receptor (S1R) dysfunction and NMDA receptor (NMDAR) hypofunction contribute to pathogenesis of schizophrenia, especially treatment-resistant schizophrenia. Several S1R agonists have been tested for its potential for schizophrenia treatment; however, its efficacy appears limited. In addition, previous studies also found that some NMDA-enhancing agents were able to augment efficacy of antipsychotics in the treatment of chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancer (NMDAE) can be better than an S1R agonist alone deserves study. Therefore, this study aims to compare an S1R agonist plus an NMDAE and an S1R agonist plus placebo in the treatment of treatment-resistant schizophrenia. The subjects are the patients with treatment-resistant schizophrenia who have responded poorly to two or more kinds of antipsychotics treatment. They keep their original treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) S1R agonist (S1RA) plus NMDAE, or (2) S1RA plus placebo. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, and 8. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of S1RA plus NMDAE and S1RA 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| S1R agonist (S1RA) plus NMDAE | Experimental | Drug: S1RA plus NMDAEAn S1R agonist plus an NMDA enhancer |
| S1R agonist (S1RA) plus placebo | Placebo comparator | Drug: S1RA plus Placebo CapAn S1R agonist plus placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
- Are resistant to adequate treatments of at least two antipsychotics (excluding clozapine)
- 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 8-week trial
- PANSS total score >70
- Hamilton Depression Rating Scale-17 items (HAMD) <7
Key exclusion criteria (4 listed)
- DSM-5 diagnosis of intellectual disability or substance (including alcohol) use disorder
- History of epilepsy, head trauma, central nervous system diseases or mental disorders other than schizophrenia (including major depressive disorder, bipolar disorders, persistent depressive disorder, obsessive-compulsive disorder)
- Pregnancy or lactation
- Inability to follow protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S1RA plus NMDAEUse of an S1R agonist plus an NMDA enhancer for the treatment of treatment-resistant schizophrenia. | Drug | S1R agonist (S1RA) plus NMDAE |
| S1RA plus Placebo CapUse of an S1R agonist plus placebo as a comparator | Drug | S1R agonist (S1RA) plus placebo |
Primary outcome
Change of Positive and Negative Syndrome Scale (PANSS)
Time frame: week 0, 2, 4, 6, 8
Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.
6 secondary outcomes
Change of scales for the Assessment of Negative Symptoms (SANS) total score
Time frame: week 0, 2, 4, 6, 8
Positive subscale, Negative subscales, and General Psychopathology subscale of PANSS
Time frame: week 0, 2, 4, 6, 8
Clinical Global Impression
Time frame: week 0, 2, 4, 6, 8
Global Assessment of Functioning
Time frame: week 0, 2, 4, 6, 8
Quality of Life Scale
Time frame: week 0, 2, 4, 6, 8
Cognitive function
Time frame: Week 0, 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Department of Psychiatry, China Medical University Hospital
Taichung, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing S1RA plus NMDAE in people with Schizophrenia, run by China Medical University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Positive and Negative Syndrome Scale (PANSS) (time frame: week 0, 2, 4, 6, 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.