SchizophreniaPhase 2NCT05240976
Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia
A Phase 2 study testing NMDAE plus AIFA in people with Schizophrenia, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant 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?
- NMDAE plus AIFA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteTaiwan
- Study dates
- 23 Feb 2022to Mar 2027
- 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 treatment-resistant to standard treatments of at least two specific antipsychotics before clozapine treatment
- Are receiving adequate trials of clozapine for more than 12 weeks but without satisfactory response
- PANSS total score ≥ 70; SANS total score ≥ 40
- 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, 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 study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.
Read the detailed description
Several lines of evidence suggest that both NMDA and inflammatory hypotheses have been implicated in schizophrenia. Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.
Therefore, this study aims to compare NMDAE plus a drug with anti-inflammatory property and NMDAE plus placebo in the treatment of ultra-resistant schizophrenia. The subjects are the patients with ultra-resistant schizophrenia who have responded poorly to clozapine treatment. They keep their original clozapine treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE plus Anti-inflammatory Agent (AIFA), or (2) NMDAE plus placebo. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. The efficacies of NMDAE plus AIFA 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) for both primary and secondary outcomes . 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 AIFA, NMDAE plus Placebo Cap
- Keywords
- Ultra-resistant schizophrenia, NMDA, Inflammation
- Medical subject headings
- Schizophrenia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMDAE plus AIFADrug
Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia.
NMDAE plus Placebo CapDrug
Use of an NMDA enhancer plus placebo as a comparator
| Study group | Role | What they receive |
|---|---|---|
| NMDAE plus Anti-inflammatory Agent (AIFA) | Experimental | An NMDA enhancer plus a drug with anti-inflammatory property Receives: Drug: NMDAE plus AIFA |
| 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 cognitive function
The measure is the composite from multiple measures. All tests have no unit. 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 of each domain (Lane HY et al, JAMA Psychiatry 2013).
Ten tests for assessing 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)
Measured: Week 0, 12
Secondary outcomes (9)
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.
As shown in "Detailed Description", "mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE) for both primary and secondary outcomes. That is, GEE is used for analyzing the changes from baseline in repeated-measure assessments by a single analysis (but not multiple analyses).
Measured: week 0, 2, 4, 6, 9, 12
Change of scale 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
Chang of 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
Change of 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
Change of 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
Change of 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
Change of 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
Change of 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
Change of 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2022
- Study start23 Feb 2022
- Primary completionFeb 2027 (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.
- 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
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Health Research Institutes, Taiwan
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05240976
- Sponsor's protocol ID
- CMUH109-REC3-043
- Status last verified
- Mar 2026
- First submitted
- 24 Jan 2022
- 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
- Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT05240976
- Acronym / sponsor ID
- CMUH109-REC3-043
- Conditions
- Schizophrenia
- Keywords
- Ultra-resistant schizophrenia, NMDA, Inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Collaborators
- National Health Research Institutes, Taiwan
- Study start
- 23 Feb 2022 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 15 Feb 2022 (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.
Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.
Detailed description
Several lines of evidence suggest that both NMDA and inflammatory hypotheses have been implicated in schizophrenia. Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.
Therefore, this study aims to compare NMDAE plus a drug with anti-inflammatory property and NMDAE plus placebo in the treatment of ultra-resistant schizophrenia. The subjects are the patients with ultra-resistant schizophrenia who have responded poorly to clozapine treatment. They keep their original clozapine treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE plus Anti-inflammatory Agent (AIFA), or (2) NMDAE plus placebo. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. The efficacies of NMDAE plus AIFA 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) for both primary and secondary outcomes . 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 |
|---|---|---|
| NMDAE plus Anti-inflammatory Agent (AIFA) | Experimental | Drug: NMDAE plus AIFAAn NMDA enhancer plus a drug with anti-inflammatory property |
| NMDAE plus Placebo | Placebo comparator | Drug: NMDAE plus Placebo CapAn NMDA enhancer plus Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
- Are treatment-resistant to standard treatments of at least two specific antipsychotics before clozapine treatment
- Are receiving adequate trials of clozapine for more than 12 weeks but without satisfactory response
- PANSS total score ≥ 70; SANS total score ≥ 40
- Have sufficient education to communicate effectively and are capable of completing the assessments of the study
Key exclusion criteria (5 listed)
- DSM-5 diagnosis of intellectual disability or substance (including alcohol) use disorder
- History of epilepsy, head trauma, 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
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 |
|---|---|---|
| NMDAE plus AIFAUse of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia. | Drug | NMDAE plus Anti-inflammatory Agent (AIFA) |
| NMDAE plus Placebo CapUse of an NMDA enhancer plus placebo as a comparator | Drug | NMDAE plus Placebo |
Primary outcome
Change of cognitive function
Time frame: Week 0, 12
The measure is the composite from multiple measures. All tests have no unit. 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 of each domain (Lane HY et al, JAMA Psychiatry 2013). Ten tests for assessing 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)
9 secondary outcomes
Change of Positive and Negative Syndrome Scale (PANSS)
Time frame: week 0, 2, 4, 6, 9, 12
Change of scale for the Assessment of Negative Symptoms (SANS) total score
Time frame: week 0, 2, 4, 6, 9, 12
Chang of positive subscale of PANSS
Time frame: week 0, 2, 4, 6, 9, 12
Change of negative subscale of PANSS
Time frame: week 0, 2, 4, 6, 9, 12
Change of general Psychopathology subscale of PANSS
Time frame: week 0, 2, 4, 6, 9, 12
Change of clinical Global Impression
Time frame: week 0, 2, 4, 6, 9, 12
Change of global Assessment of Functioning
Time frame: week 0, 2, 4, 6, 9, 12
Change of hamilton Rating Scale for Depression
Time frame: week 0, 2, 4, 6, 9, 12
Change of quality of Life Scale
Time frame: week 0, 2, 4, 6, 9, 12
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.
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 NMDAE plus AIFA 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 6 inclusion and 5 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?
Contact Hsien-Yuan Lane, M.D., Ph.D (886 4 22052121 ext. 1855, hylane@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of cognitive function (time frame: Week 0, 12). 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.