Major Depressive DisorderPhase 2NCT05136755
NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder
A Phase 2 study testing NMDAE in people with Major Depressive Disorder, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- NMDAE
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteTaiwan
- Study dates
- 25 Jan 2022to Dec 2026
- 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 MDD
- Have failed to respond to at least one antidepressant with adequate dosage and treatment duration
- Their original treatments should have been unchanged for at least 8 weeks. Some treatment-resistant patients (that is, having failed to respond to at least two different classes of antidepressants) who have started to refuse any antidepressant by themselves due to previous failure experience are also allowed, if they have already been antidepressant-free for at least 2 weeks
- 17-item Hamilton Rating Scale for Depression total score ≥ 18
- Agree to participate in the study and provide informed consent
Who cannot join
- Current substance abuse or history of substance dependence in the past 6 months
- History of epilepsy, head trauma, stroke or other serious medical or neurological illness which may interfere with the study
- Bipolar disorder, schizophrenia or other psychotic disorder
- Moderate-severe suicidal risks
- Severe cognitive impairment
- Initiating or stopping formal psychotherapy within six weeks prior to enrollment
- A history of previously received electroconvulsive therapy
- 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
Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. This study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of antidepressant nonresponders with MDD.
Read the detailed description
Major depressive disorder (MDD) is a multi-factorial disorder. Most of the current antidepressants are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. Many patients respond poorly to antidepressants and suffer from side effects. NMDA hypofunction has been implicated in the pathophysiology of depression. MDD is often associated with cognitive deficits which are not necessarily recovered by current antidepressants. The NMDA receptor regulates synaptic plasticity, memory, and cognition. Therefore, this study aims to examine the efficacy and safety as well as cognitive function improvement of NMDAE in the treatment of antidepressant nonresponders with MDD. The investigators will enroll a total of 50 antidepressant nonresponders with MDD. All patients, continuing their originally ongoing treatment throughout the study period, will be randomly assigned into either of two treatment groups: NMDAE or placebo. We will biweekly measure clinical performances using 17-item Hamilton Rating Scale for Depression, Global Assessment of Function, Perceived Stress Scale, Visual Analogue Scale for pain, Clinical Global Impression, and side effects. Quality of life and cognitive functions will be assessed at baseline and at endpoint of treatment.
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.
- Conditions
- Major Depressive Disorder
- Being tested
- NMDAE, Placebo Cap
- Keywords
- Major depressive disorder, Antidepressant nonresponders, NMDA
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMDAEDrug
Use of an NMDA enhancer for the treatment of antidepressant nonresponders with MDD
Placebo CapDrug
Use of placebo as a comparator
| Study group | Role | What they receive |
|---|---|---|
| NMDAE | Experimental | An NMDA enhancer Receives: Drug: NMDAE |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo Cap |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 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, 8
Change in Global Assessment of Functioning
Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.
Measured: Week 0, 2, 4, 6, 8
Secondary outcomes (13)
Change Change in Perceived Stress Scalein Perceived Stress Scale
Assessment of stress and anxiety symptoms Minimum value: 0, maximum value:56, the higher scores mean a worse outcome.
Measured: week 0, 2, 4, 6, 8
Visual Analogue Scale for pain
Assessment of pain Minimum value: 0, maximum value:10, the higher scores mean a worse outcome.
Measured: week 0, 2, 4, 6, 8
Clinical Global Impression
Measured: week 0, 2, 4, 6, 8
Quality of life (SF-36)
Measured: week 0, 8
Visual Continuous Performance Test
Assessment of sustained attention
Measured: week 0, 8
Wisconsin Card Sorting Test
Assessment of abstract and shift set
Measured: week 0, 8
Logical Memory Test of the Wechsler Memory Scale
Assessment of episodic memory
Measured: week 0, 8
Digit Span
Assessment of verbal working memory
Measured: week 0, 8
Spatial Span
Assessment of nonverbal working memory
Measured: week 0, 8
Category Fluency
Assessment of speed of processing
Measured: week 0, 8
Trail Marking A
Assessment of speed of processing
Measured: week 0, 8
WAIS-III Digit Symbol-Coding
Assessment of speed of processing
Measured: week 0, 8
Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0
Assessment of social cognition
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 posted29 Nov 2021
- Study start25 Jan 2022
- Primary completionNov 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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
- 50 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
- NCT05136755
- Sponsor's protocol ID
- CMUH110-REC3-123
- Status last verified
- Oct 2026
- First submitted
- 16 Nov 2021
- Last updated
- 23 Oct 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 23 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NMDA Modulation in Antidepressant Nonresponders With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05136755
- Acronym / sponsor ID
- CMUH110-REC3-123
- Conditions
- Major Depressive Disorder
- Keywords
- Major depressive disorder, Antidepressant nonresponders, NMDA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- 25 Jan 2022 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Nov 2021 (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.
Most of the current antidepressants for major depressive disorder (MDD) are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. NMDA hypofunction has been implicated in the pathophysiology of depression. This study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of antidepressant nonresponders with MDD.
Detailed description
Major depressive disorder (MDD) is a multi-factorial disorder. Most of the current antidepressants are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. Many patients respond poorly to antidepressants and suffer from side effects. NMDA hypofunction has been implicated in the pathophysiology of depression. MDD is often associated with cognitive deficits which are not necessarily recovered by current antidepressants. The NMDA receptor regulates synaptic plasticity, memory, and cognition. Therefore, this study aims to examine the efficacy and safety as well as cognitive function improvement of NMDAE in the treatment of antidepressant nonresponders with MDD. The investigators will enroll a total of 50 antidepressant nonresponders with MDD. All patients, continuing their originally ongoing treatment throughout the study period, will be randomly assigned into either of two treatment groups: NMDAE or placebo. We will biweekly measure clinical performances using 17-item Hamilton Rating Scale for Depression, Global Assessment of Function, Perceived Stress Scale, Visual Analogue Scale for pain, Clinical Global Impression, and side effects. Quality of life and cognitive functions will be assessed at baseline and at endpoint of treatment.
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.
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 | Experimental | Drug: NMDAEAn NMDA enhancer |
| Placebo | Placebo comparator | Drug: Placebo CapPlacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Have a DSM-5 (American Psychiatric Association) diagnosis of MDD
- Have failed to respond to at least one antidepressant with adequate dosage and treatment duration
- Their original treatments should have been unchanged for at least 8 weeks. Some treatment-resistant patients (that is, having failed to respond to at least two different classes of antidepressants) who have started to refuse any antidepressant by themselves due to previous failure experience are also allowed, if they have already been antidepressant-free for at least 2 weeks
- 17-item Hamilton Rating Scale for Depression total score ≥ 18
- Agree to participate in the study and provide informed consent
Key exclusion criteria (8 listed)
- Current substance abuse or history of substance dependence in the past 6 months
- History of epilepsy, head trauma, stroke or other serious medical or neurological illness which may interfere with the study
- Bipolar disorder, schizophrenia or other psychotic disorder
- Moderate-severe suicidal risks
- Severe cognitive impairment
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 |
|---|---|---|
| NMDAEUse of an NMDA enhancer for the treatment of antidepressant nonresponders with MDD | Drug | NMDAE |
| Placebo CapUse of placebo as a comparator | Drug | Placebo |
Primary outcome
Change in Hamilton Rating Scale for Depression
Time frame: week 0, 2, 4, 6, 8
Assessment of depressive symptoms Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.
Change in Global Assessment of Functioning
Time frame: Week 0, 2, 4, 6, 8
Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.
13 secondary outcomes
Change Change in Perceived Stress Scalein Perceived Stress Scale
Time frame: week 0, 2, 4, 6, 8
Visual Analogue Scale for pain
Time frame: week 0, 2, 4, 6, 8
Clinical Global Impression
Time frame: week 0, 2, 4, 6, 8
Quality of life (SF-36)
Time frame: week 0, 8
Visual Continuous Performance Test
Time frame: week 0, 8
Wisconsin Card Sorting Test
Time frame: week 0, 8
Logical Memory Test of the Wechsler Memory Scale
Time frame: week 0, 8
Digit Span
Time frame: week 0, 8
Spatial Span
Time frame: week 0, 8
Category Fluency
Time frame: week 0, 8
Trail Marking A
Time frame: week 0, 8
WAIS-III Digit Symbol-Coding
Time frame: week 0, 8
Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0
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 23 Oct 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 in people with Major Depressive Disorder, 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 5 inclusion and 8 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 23 Oct 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 in Hamilton Rating Scale for Depression (time frame: week 0, 2, 4, 6, 8). The study lists 2 primary outcomes in all. 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 23 Oct 2026.