Efficacy and Safety of Individualized Sequential Accelerated Theta Burst Stimulation in Improving Cognitive Function in Schizophrenia
2026年9月1日 更新者：Renrong Wu、Central South University
Sequential Dual-Site Accelerated Theta Burst Stimulation Targeting the Frontoparietal and Default Mode Networks for Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Study
The goal of this clinical trial is to learn if sequential dual-site accelerated theta burst stimulation (SD-aTBS) targeting the frontoparietal network and default mode network works to improve cognitive function in adults with schizophrenia. It will also learn about the safety of SD-aTBS. The main questions it aims to answer are:
Does SD-aTBS improve cognitive function in participants with schizophrenia? What are the neurobiological mechanisms (brain network and synaptic plasticity changes) underlying the effects of SD-aTBS? Researchers will compare real SD-aTBS to sham stimulation to see if SD-aTBS is effective and safe for treating cognitive impairment in schizophrenia.
Participants will:
Receive real SD-aTBS or sham stimulation for 10 consecutive working days Complete clinical symptom assessments, cognitive function tests, MRI scans, and EEG recordings at baseline, after treatment, and 1 month after treatment Undergo SV2A-PET scans at baseline and 1 month after treatment
研究概览
地位
尚未招聘
研究类型
介入性
注册 (估计的)
60
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Xingjie Peng, MD
- 电话号码：+86 151 1113 0170
- 邮箱：992348023@qq.com
研究联系人备份
- 姓名：Renrong Wu, MD
- 电话号码：+86 158 7417 9855
- 邮箱：wurenrong@csu.edu.cn
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
接受健康志愿者
不
描述
Inclusion Criteria:
- Age 18-35 years.
- Meets the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by the Structured Clinical Interview for DSM-5 (SCID-5).
- Duration of illness ≤ 8 years.
- Taking no more than 2 antipsychotic medications, with a stable antipsychotic dose for at least 4 weeks prior to enrollment, and no expected change in the medication regimen throughout the treatment and follow-up period.
（4）Presence of significant cognitive impairment (overall deficit score of MCCB plus supplementary tests ≥ 0.5).
（5）The participant and their guardian agree to participate in the study and provide written informed consent.
Exclusion Criteria:
- Current or lifetime co-occurrence of any other DSM-5 psychiatric disorder.
- Concurrent use of mood stabilizers, antidepressants, or excessive benzodiazepines (lorazepam equivalent > 2 mg/day).
- Presence of severe or acute physical illness, including a history of epilepsy, traumatic brain injury, intracranial space-occupying or infectious disease, acute cardiovascular or cerebrovascular disease, acute respiratory disease, or acute hematologic disease.
- Any contraindication to transcranial magnetic stimulation (TMS), PET scanning, or magnetic resonance imaging (MRI).
- Receipt of any other electrical or stimulation therapy within 3 months prior to enrollment.
- Current use of medications known to interact with SV2A (e.g., levetiracetam, loratadine, quinine).
Withdrawal Criteria
- Occurrence of a serious adverse event possibly related to the intervention (e.g., seizure, symptom relapse requiring immediate hospitalization).
- Onset of a new severe illness during the study (e.g., cardiovascular event, severe infection, severe hepatic or renal dysfunction).
- A change in the antipsychotic medication regimen during the study - including a dose adjustment of ≥ 25%, or a switch to a different antipsychotic medication.
- Poor adherence, inability to complete the full intervention, failure to return for follow-up as required, or inability to cooperate with the examinations and assessments.
- Pregnancy.
- Voluntary withdrawal of informed consent by the participant.
- Any other condition judged by the investigator to render the participant unable to complete the study or likely to affect the study results.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：active SD-TBS group
Participants will receive active sequential dual-site accelerated theta burst stimulation (SD-aTBS) targeting the frontoparietal network and default mode network, delivered 5 times daily for 10 consecutive working days.
|
Sequential dual-site accelerated theta burst stimulation (SD-aTBS) delivers accelerated theta burst stimulation to two individually targeted brain regions - the frontoparietal network and the default mode network - in a sequential (site-by-site) manner, with stimulation delivered 5 times daily for 10 consecutive working days.
|
|
假比较器：sham SD-TBS group
Participants will receive sham sequential dual-site accelerated theta burst stimulation (SD-aTBS) targeting the frontoparietal network and default mode network, delivered 5 times daily for 10 consecutive working days.
|
Sham sequential dual-site accelerated theta burst stimulation uses the same coil positioning and stimulation parameters as the active SD-aTBS but delivers no effective cortical stimulation, serving as a sham control
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Global cognitive function will be assessed using the mean of the standardized T-scores from 14 neuropsychological tests: the MATRICS Consensus Cognitive Battery (MCCB; 9 subtests) plus 5 supplementary tests - the Wisconsin Card Sorting Test 64-Item Version (WCST-64), the Color Trails Test I and II, the Stroop Color-Word Test, and the Paced Auditory Serial Addition Task (PASAT).
Raw scores from all 14 tests will be converted to standardized T-scores (population mean of 50, standard deviation of 10), adjusted for age, sex, education, and city of childhood and current residence.
A single composite T-score will be calculated as the mean of the 14 test T-scores.
Higher scores indicate better cognitive function.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
|
Change in Synaptic Density as Measured by [18F]SV2A-PET Standardized Uptake Value Ratio (SUVR)
大体时间：Baseline and Follow-up (Day 40 ± 3)
|
Synaptic density will be assessed using [18F]SV2A positron emission tomography (SV2A-PET).
The outcome is the change in the standardized uptake value ratio (SUVR), calculated with the centrum semiovale (white matter) as the reference region.
Higher SUVR values indicate greater synaptic density.
|
Baseline and Follow-up (Day 40 ± 3)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in Psychotic Symptom Severity as Measured by the Positive and Negative Syndrome Scale (PANSS) Total Score
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Psychiatric symptom severity will be assessed using the Positive and Negative Syndrome Scale (PANSS).
The PANSS total score ranges from 30 to 210, with higher scores indicating more severe symptoms.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
|
Change in Negative Symptom Severity as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Negative symptoms will be assessed using the Scale for the Assessment of Negative Symptoms (SANS).
The SANS total score ranges from 0 to 125, with higher scores indicating more severe negative symptoms
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
|
Change in Treatment-Emergent Adverse Event Severity as Measured by the Treatment Emergent Symptom Scale (TESS) Total Score
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Treatment-emergent adverse events will be assessed using the Treatment Emergent Symptom Scale (TESS), a 35-item clinician-rated scale.
Each item is rated for severity on a 0-4 scale (0 = absent/not applicable, 4 = severe).
The outcome is the change in TESS total severity score, with higher scores indicating greater adverse event burden.
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
|
Brain MRI Measures (High-Resolution T1-Weighted, Resting-State fMRI, Task-Based fMRI [n-back]，DTI)
大体时间：Baseline, post-intervention, and Follow-up (Day 40 ± 3)
|
Change in structural and functional MRI measures.
|
Baseline, post-intervention, and Follow-up (Day 40 ± 3)
|
|
Change in Resting-State EEG Spectral Power
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Resting-state electroencephalography (EEG) will be recorded with eyes closed.
The outcome is the change in absolute spectral power (in μV²) in the delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (30-48 Hz) frequency bands.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
|
Change in Peripheral Blood Biomarker Concentrations
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Peripheral blood samples will be collected for exploratory biomarker assessment.
The outcome is the change in the concentration of selected peripheral blood biomarkers (e.g., inflammatory cytokines, neurotrophic factors, and other candidate analytes), reported in their respective units (e.g., pg/mL).
Specific analytes will be determined and described in the results publication.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
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Incidence of Adverse Events Related to SD-aTBS
大体时间：Daily during the 10-day intervention period
|
Adverse events recorded daily through spontaneous reporting and post-treatment inquiries during the intervention period
|
Daily during the 10-day intervention period
|
|
Change in 40 Hz Auditory Steady-State Response (ASSR)
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
The auditory steady-state response (ASSR) will be elicited by 40 Hz click trains.
The outcome is the change in phase-locking factor (inter-trial coherence) and evoked power at 40 Hz.
Higher values indicate stronger 40 Hz neural synchronization.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
|
Change in Mismatch Negativity (MMN) Amplitude
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
Mismatch negativity (MMN) will be recorded during an auditory oddball paradigm.
The outcome is the change in MMN amplitude (in microvolts) at fronto-central electrodes (e.g., Fz).
Larger (more negative) MMN amplitude indicates greater pre-attentive change detection.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
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Change in P300 Event-Related Potential Amplitude
大体时间：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
|
The P300 event-related potential will be recorded during an auditory oddball paradigm.
The outcome is the change in P300 amplitude (in microvolts) at midline electrodes (e.g., Cz, Pz).
Larger P300 amplitude indicates better attentional/cognitive processing.
|
Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Renrong Wu、Second Xiangya Hospital of Central South University
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年9月30日
初级完成 (估计的)
2028年9月30日
研究完成 (估计的)
2028年9月30日
研究注册日期
首次提交
2026年8月27日
首先提交符合 QC 标准的
2026年9月1日
首次发布 (实际的)
2026年9月8日
研究记录更新
最后更新发布 (实际的)
2026年9月8日
上次提交的符合 QC 标准的更新
2026年9月1日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
其他研究编号
- LYG20260143
- 82325020 (其他赠款/资助编号：National Natural Science Foundation of China)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
De-identified individual participant data (IPD) underlying the published results will be shared, including baseline demographic and clinical characteristics, cognitive and symptom assessment scores (MCCB, PANSS, SANS, TESS), and related outcome data. Identifiable imaging (MRI, EEG, SV2A-PET) and biomarker data will only be shared in de-identified form, subject to a data use agreement and approval by the study team, to protect participant privacy.
Requests for IPD should be directed to the principal investigator
IPD 共享时间框架
After publication
IPD 共享访问标准
De-identified individual participant data underlying the published results will be shared with qualified researchers who provide a methodologically sound proposal, subject to approval by the study team and execution of a data use agreement.
IPD 共享支持信息类型
- 研究方案
- 树液
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.