A Phase 3 interventional study of [Phase 1] Clozapine and [Phase 1] Aripiprazole in Treatment-resistant Schizophrenia, sponsored by Shanghai Mental Health Center. Recruiting at 1 site in China. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by Shanghai Mental Health Center · Phase 3, Interventional, and Treatment
The goal of this study is to optimize treatment strategies for Chinese patients with treatment-resistant schizophrenia (TRS). It will compare two types of treatment:
The study aims to determine which approach provides better symptom improvement, fewer cognitive side effects, and greater overall safety. The results may provide important clinical evidence to guide future treatment decisions for patients with TRS.
This is a sequential, assessor-blinded randomized controlled trial in Chinese patients with treatment-resistant schizophrenia (TRS). The study consists of two treatment components.
First, clozapine-naive TRS participants will enter an 8-week pharmacological optimization phase and be assigned to one of three treatment groups: clozapine monotherapy, clozapine plus amisulpride, or clozapine plus aripiprazole.
Second, eligible participants will enter a 4-week assessor-blinded neuromodulation phase comparing modified electroconvulsive therapy (MECT) and magnetic seizure therapy (MST). Participants for this phase are either (1) patients who have previously received clozapine and are hospitalized due to symptom exacerbation, or (2) participants who completed the pharmacological optimization phase and showed inadequate response, defined as less than 25% reduction in PANSS total score at Week 8.
The study is expected to provide evidence on the effectiveness, cognitive safety, and overall tolerability of these treatments for TRS. The project has important clinical significance.
53 studies on the registry are indexed under Schizophrenia, Treatment-Resistant; 22 are open to participants now.
This study's planned enrollment of 300 is above the median of 60 across 46 interventional studies indexed under Schizophrenia, Treatment-Resistant.
Browse Schizophrenia, Treatment-Resistant studies →Shanghai Mental Health Center is the lead sponsor of 272 studies on the registry; 91 are open to participants now.
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General inclusion criteria applicable to all participants:
Eligibility for the pharmacological optimization phase:
Eligibility for the neuromodulation phase:
Participants may enter the neuromodulation phase through either of the following pathways:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Phase 1 of the trial is an 8-week randomized controlled trial(RCT); patients will be randomly assigned to one of three treatment arms with different oral antipsychotics, one is Clozapine Monotherapy. Non-responders in phase 1 will switch to phase 2.
Drug: [Phase 1] Clozapine
Phase 1 of the trial is a 8-week randomized controlled trial(RCT); patients will be randomly assigned to one of three treatment arms with different oral antipsychotics, one of which is 'Clozapine + Aripiprazole'. Non-responders in phase 1 will switch to phase 2.
Drug: [Phase 1] Clozapine · Drug: [Phase 1] Aripiprazole
Phase 1 of the trial is a 8-week randomized controlled trial(RCT); patients will be randomly assigned to one of three treatment arms with different oral antipsychotics, one of which is 'Clozapine + Amisulpride'. Non-responders in phase 1 will switch to phase 2.
Drug: [Phase 1] Clozapine · Drug: [Phase 1] Amisulpride
CRS participants will receive modified electroconvulsive therapy while maintaining stable pharmacological treatment. The treatment course consists of 3 times per week for the first two weeks, followed by 2 times per week for the next two weeks, totaling 10 times per month, which is the same number of treatment sessions as the MST group.
Device: [Phase 2] Modified Electroconvulsive Therapy (MECT)
CRS participants will receive magnetic seizure therapy while maintaining stable pharmacological treatment. The treatment course consists of 3 times per week for the first two weeks, followed by 2 times per week for the next two weeks, totaling 10 times per month, which is the same number of treatment sessions as the MECT group.
Device: [Phase 2] Magnetic Seizure Therapy (MST)
Initial dose: 25-50 mg/day orally. Clozapine will be individually titrated over 8 weeks, with a usual target dose of 300-450 mg/day and a target steady-state trough plasma concentration of ≥350 ng/mL. Plasma clozapine concentration will be assessed at Week 4. If the concentration is \<350 ng/mL, the dose will be further increased as clinically tolerated. A dose of ≥300 mg/day is not required if the target plasma concentration is achieved at a lower dose. Participants who cannot reach either 300 mg/day or the target plasma concentration because of intolerance may remain on their maximum tolerated dose below 300 mg/day.
Also known as: Clo
Initial dose: 5-10 mg/day. Aripiprazole recommended dosage:10-15 mg/day. dosage form:po.duration:8 weeks
Also known as: Ari
Initial dose: 200-400 mg/day. Amisulpride recommended dosage: 400-800 mg/day. dosage form:po.duration:8 weeks
Also known as: Ami
MECT will be administered using a Thymatron System IV device. The electrical charge will be determined according to the participant's age and body weight, with treatment parameters adjusted according to the study protocol and clinical response. Participants will continue the pharmacotherapy regimen received before Phase 2. Medication doses will remain stable whenever clinically feasible; changes will be permitted only when clinically necessary for safety or tolerability and will be documented.
Also known as: MECT
MST will be administered using a MagPro X100 magnetic stimulator equipped with the MagOption MST module. The stimulation frequency will be set at 100 Hz and output intensity at 100% of device output. Stimulation duration will be titrated according to the study protocol and individual participant response. Participants will continue the pharmacotherapy regimen received before Phase 2. Medication doses will remain stable whenever clinically feasible; changes will be permitted only when clinically necessary for safety or tolerability and will be documented.
Also known as: MST
PANSS reduction rate at Week 8 during the pharmacological optimization phase
Percentage reduction in Positive and Negative Syndrome Scale total score from baseline to Week 8. The PANSS scale consists of 30 items, and each item is rated on a 7-point scale, ranging from 1 (no symptoms) to 7 (extremely severe). The PANSS reduction rate is calculated as: (baseline PANSS total score - Week 8 PANSS total score) / (baseline PANSS total score - 30) × 100%.
Time frame: Baseline of pharmacological optimization phase and Week 8
PANSS reduction rate at Week 4 during the neuromodulation phase
Percentage reduction in PANSS total score from baseline of the neuromodulation phase to Week 4. The PANSS scale consists of 30 items, and each item is rated on a 7-point scale, ranging from 1 (no symptoms) to 7 (extremely severe). The PANSS reduction rate is calculated as: (baseline PANSS total score - Week 4 PANSS total score) / (baseline PANSS total score - 30) × 100%.
Time frame: Baseline of neuromodulation phase and Week 4
Change in CGI-S score
Change in Clinical Global Impression-Severity (CGI-S) score from baseline to the end of assigned treatment. The scale provides an assessment of both disease severity and overall efficacy.The severity of the disease was scored on an eight-point scale ranging from 0 (not rated) to 7 (extremely severe). The overall efficacy was assessed on an 8-point scale ranging from 0 (not assessed) to 7 (significant deterioration).
Time frame: Pharmacological optimization: baseline and Week 8; Neuromodulation: baseline and Week 4.
Trajectory of PANSS total score improvement during the neuromodulation phase
Rate of change in Positive and Negative Syndrome Scale total score during the 4-week neuromodulation treatment course. The PANSS scale consists of 30 items, and each item is rated on a 7-point scale, ranging from 1 (no symptoms) to 7 (extremely severe). Repeated PANSS assessments will be used to compare the trajectory and speed of symptom improvement between the MECT and MST groups.
Time frame: Baseline of the neuromodulation phase and weekly during the 4-week neuromodulation treatment course
Change in AMT specificity score during the neuromodulation phase
Change in Autobiographical Memory Test(AMT) specificity score from baseline of the neuromodulation phase to Week 4. The AMT specificity score is defined as the number of specific autobiographical memories retrieved in response to 12 cue words, with scores ranging from 0 to 12 and higher scores indicating better autobiographical memory specificity. Change is calculated as Week 4 AMT specificity score minus baseline AMT specificity score; negative values indicate decline in autobiographical memory specificity.
Time frame: Baseline of the neuromodulation phase and Week 4
Change from baseline in cognitive function: MCCB
MATRICS consensus cognitive battery (MCCB) consists of 10 tests that assess cognitive performance in 7 domains, including processing speed, attention/vigilance, working memory, verbal memory, visual learning, reasoning and problem solving, and social cognition.The MCCB T-score is calculated based on a Chinese community sample, with a normative mean of 50 and a standard deviation of 10. Higher scores indicate a better neurocognitive outcome.
Time frame: Baseline, Month 1, and Month 2 during the pharmacological optimization phase; and Week 4 of the neuromodulation phase.
Change in visuospatial working memory during the neuromodulation phase
Change in visuospatial working memory from baseline to Week 4, assessed using the Wechsler Memory Scale-III Spatial Span subtest (WMS III). The WMS III total score ranges from 0 to 32, with higher scores indicating better visuospatial working memory performance.
Time frame: Baseline of the neuromodulation phase and weekly during the 4-week neuromodulation phase
Change in visual learning during the neuromodulation phase
Change in visual learning from baseline to Week 4, assessed using the Brief Visuospatial Memory Test-Revised (BVMT-R).The BVMT-R total recall score ranges from 0 to 36, where higher scores indicate better visual learning ability.
Time frame: Baseline of the neuromodulation phase and weekly during the 4-week neuromodulation phase
Change in personal and social functioning
Change in Personal and Social Performance Scale(PSP) score from baseline to the end of the corresponding treatment phase.The PSP score ranges from 0 to 100, where higher scores indicate better personal and social functioning.
Time frame: Baseline, Week 8 of the pharmacological optimization phase and Week 4 of the neuromodulation phase
Extrapyramidal adverse effects: The Barnes Akathisia Scale (BAS)
The Barnes Akathisia Scale (BAS) will be used to evaluate objective performance and subjective experience of akathisia, scored from 0 to 3, and the overall clinical evaluation of akathisia is scored from 0 to 5. The higher scores mean a more serious side effect.
Time frame: Baseline, Week 4, Week 8 during the pharmacological optimization phase and Week 1, Week 2, Week 3, Week 4 during the neuromodulation phase
Extrapyramidal adverse effects: Simpson-Angus Extrapyramidal Side Effects Scale (SAS)
Simpson-Angus Extrapyramidal Side Effects Scale (SAS) consists of 10 items, each scored from 0 to 4. The higher scores mean a more serious side effect.
Time frame: Baseline, Week 4, Week 8 during the pharmacological optimization phase and Week 1, Week 2, Week 3, Week 4 during the neuromodulation phase
Extrapyramidal adverse effects: Abnormal Involuntary Movement Scale (AIMS)
Abnormal Involuntary Movement Scale (AIMS) consists of 12 items. The first 10 of 12 items is scored from 0 to 4, and the last 2 is scored from 0 to 1. The higher scores mean the more obvious abnormal involuntary movement.
Time frame: Baseline, Week 4, Week 8 during the pharmacological optimization phase and Week 1, Week 2, Week 3, Week 4 during the neuromodulation phase
Plan to share: No — Individual participant data will not be shared because the study involves sensitive clinical, cognitive, imaging, and biological data from patients with schizophrenia, and data sharing is limited by participant consent and institutional ethics requirements. Only aggregate study results will be reported.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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