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
調査の概要
状態
まだ募集していません
研究の種類
介入
入学 (推定)
60
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Xingjie Peng, MD
- 電話番号：+86 151 1113 0170
- メール：992348023@qq.com
研究連絡先のバックアップ
- 名前：Renrong Wu, MD
- 電話番号：+86 158 7417 9855
- メール：wurenrong@csu.edu.cn
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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.
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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.
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偽コンパレータ：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.
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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
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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Change in Synaptic Density as Measured by [18F]SV2A-PET Standardized Uptake Value Ratio (SUVR)
時間枠：Baseline and Follow-up (Day 40 ± 3)
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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.
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Baseline and Follow-up (Day 40 ± 3)
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Psychotic Symptom Severity as Measured by the Positive and Negative Syndrome Scale (PANSS) Total Score
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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Change in Negative Symptom Severity as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Total Score
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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Change in Treatment-Emergent Adverse Event Severity as Measured by the Treatment Emergent Symptom Scale (TESS) Total Score
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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)
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Brain MRI Measures (High-Resolution T1-Weighted, Resting-State fMRI, Task-Based fMRI [n-back]，DTI)
時間枠：Baseline, post-intervention, and Follow-up (Day 40 ± 3)
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Change in structural and functional MRI measures.
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Baseline, post-intervention, and Follow-up (Day 40 ± 3)
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Change in Resting-State EEG Spectral Power
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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Change in Peripheral Blood Biomarker Concentrations
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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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
時間枠：Daily during the 10-day intervention period
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Adverse events recorded daily through spontaneous reporting and post-treatment inquiries during the intervention period
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Daily during the 10-day intervention period
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Change in 40 Hz Auditory Steady-State Response (ASSR)
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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Change in Mismatch Negativity (MMN) Amplitude
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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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
時間枠：Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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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.
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Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Renrong Wu、Second Xiangya Hospital of Central South University
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年9月30日
一次修了 (推定)
2028年9月30日
研究の完了 (推定)
2028年9月30日
試験登録日
最初に提出
2026年8月27日
QC基準を満たした最初の提出物
2026年9月1日
最初の投稿 (実際)
2026年9月8日
学習記録の更新
投稿された最後の更新 (実際)
2026年9月8日
QC基準を満たした最後の更新が送信されました
2026年9月1日
最終確認日
2026年8月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- LYG20260143
- 82325020 (その他の助成金/資金番号：National Natural Science Foundation of China)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
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 共有時間枠
After publication
IPD 共有アクセス基準
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 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
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米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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