Development of a Multi-target Transcranial Magnetic Intervention Technique for Negative Symptoms of Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Change in severity of negative symptoms before and after TBS intervention, i.e., change in Positive and Negative Syndrome Scale - Negative subscale (PANSS-N)
研究概览
简要总结
This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the right orbitofrontal cortex (R-OFC), left dorsolateral prefrontal cortex (L-DLPFC), and left inferior parietal lobule (L-IPL) for negative symptoms of schizophrenia.
详细描述
Schizophrenia is a chronic and severe mental disorder. Although antipsychotic medications are effective for positive symptoms, they offer limited improvement for negative symptoms and cognitive deficits. Effective treatments for these symptoms are still lacking. To address current clinical bottlenecks, there is an urgent need to develop novel, effective treatment strategies. Repetitive transcranial magnetic stimulation (rTMS) is a recently developed neuromodulation technique. The latest evidence-based guidelines indicate that the level of evidence for rTMS in treating schizophrenia remains low (i.e., Level C evidence, possibly effective). However, the critical parameter of target selection has not received sufficient attention. This randomized controlled trial (RCT) is the first to evaluate the efficacy and safety of a multi-target TMS protocol targeting the Right Orbitofrontal Cortex (R-OFC), Left Dorsolateral Prefrontal Cortex (L-DLPFC), and Left Inferior Parietal Lobe (L-IPL) for negative symptoms of schizophrenia. MRI-guided neuronavigation will be used to localize targets in each subject. The intensity of TMS stimulations is set to 80-120% of resting motor threshold (RMT). A total of 50 TMS sessions will be administered. The stimulation sequence will be R-OFC (1 Hz) → L-DLPFC (iTBS) → L-IPL (iTBS). The first target (R-OFC) will receive 720 pulses at 1 Hz, while the second and third targets (L-DLPFC and L-IPL) will each receive 900 pulses of iTBS. Five sessions will be delivered per day for 10 consecutive working days, with a 60-minute interval between sessions. Clinical assessments, cognitive evaluations, and resting-state functional Magnetic Resonance Imaging (MRI) scans will be performed before and after TMS treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Outpatients or inpatients at the Department of Psychiatry, Shanghai Mental Health Center;
- •Meet the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for first-episode schizophrenia (diagnosed using the Structured Clinical Interview for DSM-5, SCID-5); disease duration less than 5 years at enrollment;
- •Male or female aged 16-45 years;
- •Education duration ≥ 9 years;
- •Stable medication regimen for at least 6 weeks prior to baseline visit and throughout the study period; psychiatric symptoms generally stable within 1 month prior to baseline visit;
- •Participants and their guardians can understand and sign written informed consent;
- •Total score on the PANSS Negative Symptom subscale (PANSS-N) > 15, and at least one item score ≥ 3.
排除标准
- •Current or lifetime psychiatric disorders as determined by SCID-5 assessment;
- •Severe or unstable physical illnesses, including: neurological disorders (delirium, dementia, stroke, epilepsy, migraine, etc.), congestive heart failure, angina pectoris, myocardial infarction, arrhythmia, hypertension, hyperglycemia, malignant tumors, and immunocompromised conditions;
- •Alcohol abuse within 30 days prior to the study or alcohol/drug dependence within 6 months prior to the study; participation in any clinical trial within 30 days prior to baseline;
- •Pregnant or breastfeeding women;
- •Intellectual disability (IQ < 70);
- •No history of modified electroconvulsive therapy (mECT) within the past 6 months.
研究组 & 干预措施
TMS intervention targeting multiple targets
干预措施: repetitive transcranial magnetic stimulation (rTMS) (Device)
Control group
Same targets, sham TMS
干预措施: repetitive transcranial magnetic stimulation (rTMS) (Device)
结局指标
主要结局
Change in severity of negative symptoms before and after TBS intervention, i.e., change in Positive and Negative Syndrome Scale - Negative subscale (PANSS-N)
时间窗: Negative symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and at 1 week (Day 21), 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TBS treatment.
Schizophrenia negative symptoms assessed using Positive and Negative Syndrome Scale - Negative subscale (PANSS-N) Minimum value: 7 (each of the 7 items scored 1 = absent) Maximum value: 49 (each of the 7 items scored 7 = extreme) Higher score indicates: Worse outcome (greater severity of negative symptoms)
Change in severity of negative symptoms before and after TMS intervention, i.e., change in Positive and Negative Syndrome Scale - Negative subscale (PANSS-N)
时间窗: Negative symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.
Schizophrenia negative symptoms assessed using Positive and Negative Syndrome Scale - Negative subscale (PANSS-N) Minimum value: 7 (each of the 7 items scored 1 = absent) Maximum value: 49 (each of the 7 items scored 7 = extreme) Higher score indicates: Worse outcome (greater severity of negative symptoms)
次要结局
- Change in cognitive function scores before and after intervention(MATRICS Consensus Cognitive Battery (MCCB) will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and 4 weeks ( Day 42) after completion of TBS treatment.)
- Change in positive symptom scores before and after intervention(Positive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and at 1 week (Day 21), 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TBS treatment.)
- Change in general symptom scores before and after intervention(General symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and at 1 week (Day 21), 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TBS treatment.)
- Change in anxiety symptoms before and after intervention(Anxiety symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and at 1 week (Day 21), 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TBS treatment.)
- Depressive symptoms changes(Depressive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and at 1 week (Day 21), 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TBS treatment.)
- Safety as measured by number of participants with Adverse Events(Record the adverse events reported on that day after completing the day's TBS treatment. This should be done every day during the treatment period (Day 0 - Day 14))
- Resting-state functional MRI (rsfMRI) scan(Resting-state functional MRI will be measured at baseline (Day-4±2), immediately after the 50th session of TBS (Day 14), and 4 weeks ( Day 42) after completion of TBS treatment.)
- Change in cognitive function scores before and after intervention(MATRICS Consensus Cognitive Battery (MCCB) will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and 4 weeks ( Day 42) after completion of TMS treatment.)
- Change in positive symptom scores before and after intervention(Positive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.)
- Change in general symptom scores before and after intervention(General symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.)
- Change in anxiety symptoms before and after intervention(Anxiety symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.)
- Depressive symptoms changes(Depressive symptoms will be measured at baseline (Day-4±2), immediately after the 50th session of TMS (Day 14), and at 2 weeks (Day 28), and 4 weeks ( Day 42) after completion of TMS treatment.)
- Safety as measured by number of participants with Adverse Events(Record the adverse events reported on that day after completing the day's TMS treatment. This should be done every day during the treatment period (Day 0 - Day 14))
- Resting-state functional MRI (rsfMRI) scan(Resting-state functional MRI will be measured at baseline (Day-4±2), and immediately after the 50th session of TMS (Day 14).)