Schizo Affective Disorder, Schizophrenia Disorders
Conditions
Keywords
Schizophrenia, Stereoelectroencephalography, Neuroimaging, deep brain stimulation
Brief summary
This is a prospective, randomized, interventional study designed to evaluate the efficacy and safety of SEEG-guided deep brain stimulation (DBS) for symptom improvement in patients with treatment-resistant schizophrenia. Using stereo-electroencephalography (SEEG) to record brain activity, we will identify specific abnormal electrophysiological targets and signal features associated with clinical symptoms, followed by a 12-month open-label stimulation period. The study is conducted in three stages: Stage 1 consists of SEEG brain mapping, screening of intervention targets, and optimization of stimulation parameters; Stage 2 consists of DBS implantation surgery and further optimization of stimulation parameters; Stage 3 is a randomized crossover treatment phase, followed by an open-label treatment period.
Detailed description
This clinical trial aims to systematically evaluate the efficacy and safety of SEEG-guided target screening combined with individualized deep brain stimulation (DBS) for treatment-refractory schizophrenia. The study first employs Stereoelectroencephalography (SEEG) electrodes as the core tool to establish a personalized, minimally invasive neuromodulation surgical framework. After SEEG electrode implantation, researchers will collect and analyze high-spatiotemporal-resolution electrophysiological data during both resting-state and task-state conditions, as well as identify characteristic electrophysiological biomarkers that correlate with clinical symptoms. Secondly, electrical stimulation is delivered through the SEEG contacts to functionally verify candidate targets in different brain regions. By stimulating specific targets and observing immediate symptomatic or physiological responses, we validate the effects on neural circuits and confirm their functional relevance prior to any permanent intervention. For targets that show preliminary efficacy, we further apply externalized chronic stimulation to continuously monitor symptom improvement and potential adverse effects. After determine the optimal targets and the intervention is confirmed to be both effective and safe, we implant a permanent brain pacemaker (DBS device). During the efficacy follow-up phase, we employ a randomized crossover design, which is then followed by an open-label period. These two stages enable thorough assessment of clinical efficacy. Meanwhile, we also collect multidimensional data (clinical symptoms, cognition, and neuroimaging) to explore the circuit mechanisms of stimulation.
Interventions
PROCEDURESEEG implantation
Phase 1 involves the stereotactic implantation of Stereoelectroencephalography (SEEG) electrodes. Following implantation, comprehensive electrophysiological monitoring is conducted, including resting-state and task-state recordings, as well as acute electrical stimulation mapping. This process aims to identify the specific pathological neural circuits and electrophysiological biomarkers associated with the patient's individual psychotic symptoms.
DEVICEDeep brain stimulation
Phase 2 involves individualized deep brain stimulation (DBS). Instead of relying solely on standardized anatomical landmarks, the DBS targets and parameters are precisely customized based on the individualized data acquired during the SEEG mapping phase.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Meets the International Classification of Diseases, 10th Revision (ICD-10) diagnostic criteria for schizophrenia. * Male or female, aged 18 to 55 years, with stable vital signs. * Currently presents with prominent psychotic symptoms, assessed as moderate or severe by the Positive and Negative Syndrome Scale (PANSS) or other equivalent scales. * Exhibits impaired social functioning, assessed as moderate or severe impairment by the Social and Occupational Functioning Assessment Scale (SOFAS) or other equivalent scales. * Has a history of sequential treatment with at least two antipsychotic medications of different chemical structures known for strong efficacy against positive symptoms. Treatment must have been at an adequate dose and for an adequate duration (continuous treatment at a therapeutic dose for more than 6 weeks per medication), with good treatment adherence. * Has been on a stable antipsychotic medication regimen for at least one month prior to enrollment. * Capable and willing to provide written informed consent. * Demonstrates good compliance and is able to cooperate with all follow-up procedures.
Exclusion criteria
* Diagnosed with any psychiatric disorder other than schizophrenia. * Presence of a severe personality disorder. * History of severe neurological diseases, such as seizures or hemorrhagic stroke. * Presence of structural brain abnormalities. * Previous history of stereotactic neurosurgery. * Contraindications to general anesthesia or stereotactic neurosurgery. * Any current or anticipated condition-including medical, psychological, social, familial support, or geographical factors-that might compromise patient safety or interfere with successful participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction Rate of PANSS Positive Subscale or SAPS | Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation. | Positive symptoms are assessed using either the Positive and Negative Syndrome Scale (PANSS) positive subscale (P1-P7) or the Scale for the Assessment of Positive Symptoms (SAPS). The PANSS evaluates positive, negative, and general psychopathology symptoms (total score range: 30-210). The SAPS evaluates hallucinations, delusions, bizarre behavior, and positive formal thought disorder. For both scales, higher scores indicate greater symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction Rate of Auditory Hallucinations (Assessed by PSYRATS-AH) | Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation. | The severity of auditory hallucinations is assessed using the Psychotic Symptom Rating Scales - Auditory Hallucinations subscale (PSYRATS-AH). Higher scores indicate greater symptom severity. |
| Reduction Rate of Delusions (Assessed by PSYRATS-D) | Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation. | The severity of delusions is assessed using the Psychotic Symptom Rating Scales - Delusions subscale (PSYRATS-D). Higher scores indicate greater symptom severity. |
| Reduction Rate of Depressive Symptoms (Assessed by HAMD) | Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation. | The severity of depression is assessed using the Hamilton Depression Rating Scale (HAMD). Higher scores indicate greater severity of depressive symptoms. The reduction rate will be calculated based on the change in the HAMD total score from baseline to each follow-up time point. |
| Reduction Rate of Anxiety Symptoms (Assessed by HAMA) | Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation. | The severity of anxiety is assessed using the Hamilton Anxiety Rating Scale (HAMA). Higher scores indicate greater severity of anxiety symptoms. The reduction rate will be calculated based on the change in the HAMA total score from baseline to each follow-up time point. |
| Improvement Rate of Cognitive Function (Assessed by MoCA) | Baseline (pre-operation), 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks post-operation. | General cognitive performance is assessed using the Montreal Cognitive Assessment (MoCA). The MoCA total score ranges from 0 to 30, with higher scores indicating better cognitive function. Unlike symptom rating scales, the outcome here focuses on the positive percentage change (improvement rate) or absolute point increase in the MoCA total score from baseline to each follow-up time point. |
Countries
China
Contacts
CONTACTShuo Ma, PhD
Outcome results
None listed