dACC-Targeted Temporal Interference for Negative and Cognitive Symptoms in Schizophrenia
2026年8月19日 更新者：Fan Wu、Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University
A Randomized Controlled Trial Exploring the Efficacy of Temporal Interference Stimulation for Negative Symptoms and Cognitive Impairment in Schizophrenia
This randomized, double-blind, sham-controlled trial aims to evaluate the efficacy and safety of dorsal anterior cingulate cortex-targeted temporal interference stimulation in individuals with schizophrenia.
Participants will be randomly assigned to receive either active or sham stimulation for 10 sessions over two consecutive weeks.
The primary outcome is the change in negative symptoms, assessed using the Negative Symptom Subscale of the Positive and Negative Syndrome Scale.
Cognitive performance, detailed dimensions of negative symptoms, psychosocial functioning, quality of life, and treatment-related adverse events will also be evaluated.
Neuroimaging assessments will be conducted before and after the intervention to explore potential neural mechanisms underlying the clinical effects of temporal interference stimulation.
調査の概要
状態
募集
条件
詳細な説明
Background and Scientific Rationale Persistent negative symptoms and cognitive difficulties remain major barriers to recovery in schizophrenia, often showing insufficient improvement with standard antipsychotic treatments. Transcranial temporal interference stimulation (tTIS) represents a novel non-invasive neuromodulation technique capable of reaching deeper brain structures without direct activation of overlying superficial cortical tissue. This trial focuses on targeting the dorsal anterior cingulate cortex (dACC), a critical node in the prefrontal-cingulate-striatal network involved in cognitive control, performance monitoring, and motivational processes. Study Design and Participants This study is a parallel-group, participant- and outcome-assessor-blinded, sham-controlled randomized clinical trial. A total of 74 eligible participants with a confirmed diagnosis of schizophrenia, who exhibit clinically meaningful negative symptoms and objective cognitive impairment, will be enrolled. Participants will be randomly assigned in a 1:1 ratio to receive either active dACC-targeted tTIS or sham stimulation.
ntervention ProceduresActive tTIS: Stimulation is delivered via a NervioX-1000 stimulator using two scalp electrode pairs targeting the dACC. The system applies two high-frequency carrier currents (2000 Hz and 2006 Hz) to generate a lower-frequency 6-Hz amplitude-modulated envelope field at the target region. Current intensity is titrated to participant tolerance and does not exceed 3.6 mA per channel. The treatment course consists of ten 30-minute sessions administered on consecutive weekdays over two weeks. Sham tTIS: The control group receives a sensory-matched simulation utilizing identical electrode montages and visit schedules. To ensure the integrity of the double-blind design, the sham condition features only brief ramp-up and ramp-down periods at the beginning and end of the session to mimic the transient scalp sensations of active treatment, with no continuous current delivered in between. Individualized Optimization: Prior to the intervention, participant-specific finite-element head models are derived from T1-weighted anatomical MRI scans to optimize dACC targeting, guiding candidate electrode positions and electric-field distributions.
Assessments and Outcomes Comprehensive evaluations are conducted at three specific time points: before the first stimulation session (baseline/T0), immediately after the 10-session treatment course (T1), and 4 weeks after treatment completion (T2). Primary Endpoint: The primary objective is to evaluate the change in negative symptom severity, operationalized as the clinician-rated Positive and Negative Syndrome Scale negative symptom subscale (PANSS-NS) score. Secondary Clinical Endpoints: Key secondary measures include overall neurocognitive functioning assessed by the Brief Assessment of Cognition in Schizophrenia (BACS) composite z-score and the dimensional structure of negative symptoms via the Scale for the Assessment of Negative Symptoms (SANS) total score. Broader evaluations incorporate measures of general psychopathology, apathy, anhedonia, social functioning, depression, anxiety, and sleep quality. Behavioral Tracking: Cognitive control, conflict processing, and response inhibition are objectively quantified using computerized Go/No-Go paradigms and the Stroop color-word task. Mechanistic Neuroimaging Exploration: Resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) data are acquired pre- and post-intervention. These exploratory analyses aim to investigate treatment-related neural changes, tracking alterations in spontaneous brain activity and structural/functional connectivity to provide preliminary evidence of circuit-level mechanisms.
研究の種類
介入
入学 (推定)
74
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：Fan Wu
- 電話番号：86+17621766869
- メール：butterfly2402@163.com
研究連絡先のバックアップ
- 名前：Hengfen Gong, MS
- メール：gonghf@shspdjw.com
研究場所
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Shanghai、中国
- 募集
- Shanghai Pudong New Area Mental Health Center
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コンタクト：
- Wufan
- 電話番号：021-68306699*1222
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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
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
All of the following criteria must be satisfied for enrolment:
- A confirmed diagnosis of schizophrenia established according to the criteria set forth in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
- Age between 18 and 65 years, regardless of sex, with completion of at least junior secondary education and the capacity to undergo neurocognitive testing;
- Clinically meaningful negative symptoms, operationalized as a PANSS negative symptom subscale (PANSS-NS) total score ≥ 20 with a rating of ≥ 3 on a minimum of one individual PANSS-NS item ; the PANSS positive symptom subscale score must additionally not exceed 19;
- Objective cognitive impairment evidenced by an age- and sex-adjusted composite z-score of ≤ -1.0 on the Chinese version of the Brief Assessment of Cognition in Schizophrenia (BACS), reflecting performance at least one standard deviation below normative values derived from Mandarin-speaking populations;
- Maintenance on an unchanged antipsychotic regimen - with no modification to medication type or dose - for at least 30 days prior to informed consent and continuing throughout the trial;
- Voluntary agreement to participate, documented by written informed consent following thorough explanation of study objectives and procedures; where applicable, a legally authorized representative may provide or co-sign consent.
Exclusion Criteria:
Individuals will be ineligible if any of the following conditions apply:
- A concurrent psychiatric diagnosis requiring active clinical management, including but not limited to major depressive episode or bipolar disorder, or the presence of a comorbid neurological disorder or serious physical illness;
- Current or past substance use disorder, encompassing problematic consumption of alcohol or illicit substances;
- A documented seizure disorder or marked electroencephalographic abnormalities, particularly epileptiform activity;
- Evidence of structural brain pathology, including organic lesions, prior traumatic brain injury, or previous neurosurgical intervention;
- Presence of ferromagnetic implants or any other contraindication to MRI or tTIS exposure, including intracranial metallic clips, implanted cardiac devices, or cochlear implants;
- Current use of glucocorticoids or other pharmacological agents known to meaningfully alter cortical excitability;
- Prior exposure to any neuromodulatory intervention - including modified electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (TMS), or transcranial direct current stimulation (tDCS) - within the 30 days preceding enrolment.
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：ダブル
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 tTIS
Participants assigned to this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the dorsal anterior cingulate cortex (dACC).
The stimulation will be delivered using two scalp electrode pairs operating at 2000 Hz and 2006 Hz, resulting in a 6-Hz envelope frequency.
Current intensity will be titrated to participant tolerance and will not exceed 3.6 mA per channel.
The intervention will be administered for 30 minutes per session across 10 consecutive weekdays.
Each session begins with a 10-second current ramp-up and ends with a 10-second ramp-down.
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Participants will receive active temporal interference stimulation targeting the dorsal anterior cingulate cortex.
Two high-frequency alternating currents at 2000 Hz and 2006 Hz will be delivered using an individualized electrode configuration determined by electric field modeling.
Each session will last 30 minutes.
Treatment will be administered five times per week for two consecutive weeks, for a total of 10 sessions.
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偽コンパレータ：Sham tTIS
Participants assigned to this arm will receive sham transcranial temporal interference stimulation (tTIS).
The sham condition will mirror the active intervention with respect to electrode montage, visit schedule, and session length (30 minutes per session across 10 consecutive weekdays).
To reproduce the transient scalp sensations associated with treatment initiation and termination, brief ramp-up and ramp-down periods will be applied at the beginning and end of each visit.
Between these two phases, no continuous current will be delivered.
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Participants will receive sham temporal interference stimulation using the same electrode placement and session schedule as the active stimulation group.
Brief ramp-up and ramp-down periods will be applied to mimic the sensations associated with active stimulation, but sustained temporal interference stimulation will not be delivered.
Each session will last 30 minutes.
Treatment will be administered five times per week for two consecutive weeks, for a total of 10 sessions.
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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 the Positive and Negative Syndrome Scale Negative Symptom Subscale Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The Positive and Negative Syndrome Scale Negative Symptom Subscale (PANSS-NS) consists of 7 items.
Each item is rated from 1 to 7, yielding a total score ranging from 7 to 49.
Higher scores indicate greater severity of negative symptoms.
The change from baseline to immediately after the intervention will be compared between the active and sham stimulation groups.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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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 the Brief Assessment of Cognition in Schizophrenia Composite Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The Brief Assessment of Cognition in Schizophrenia (BACS) is a multidomain battery assessing overall neurocognitive functioning, including verbal learning and memory, working memory, psychomotor speed, verbal fluency, sustained attention and processing speed, and executive function.
The constituent subtests include the List Learning Test, Digit Sequencing Task, Token Motor Task, Category Instances and Controlled Oral Word Association Test, Symbol Coding Task, and Tower of London Test.
Domain scores are aggregated into a single composite z-score standardized against age- and sex-matched normative data.
Lower values reflect greater cognitive impairment.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in the Scale for the Assessment of Negative Symptoms Total Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The Scale for the Assessment of Negative Symptoms (SANS) provides a detailed characterization of negative symptomatology.
It comprises 25 clinician-rated items spanning five domains: affective flattening or blunting, alogia, avolition-apathy, anhedonia-asociality, and attentional impairment.
Each item is rated on a six-point scale ranging from 0 to 5. The item scores are summed to generate a total score, where higher values denote a more severe negative symptom profile.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in the Temporal Experience of Pleasure Scale Total Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The Temporal Experience of Pleasure Scale (TEPS) is used to evaluate hedonic experience by separately indexing the anticipatory and consummatory components of pleasure.
The scale consists of 20 items, with each item rated on a six-point Likert scale ranging from 1 ("very false for me") to 6 ("very true for me").
Following the reverse-scoring of designated items, responses are summed to yield a total score, where lower values indicate greater anhedonia.
Therefore, higher scores indicate a better outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in the Personal and Social Performance Scale Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The Personal and Social Performance Scale (PSP) is a clinician-administered tool used to evaluate real-world social functioning.
It appraises four behavioral domains: engagement in socially constructive activities, interpersonal relationships, self-care, and disruptive or aggressive conduct.
The total score spans from 1 to 100, with higher scores reflecting superior functional status.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in the World Health Organization Quality of Life-BREF Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Subjective quality of life will be assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF).
This multidimensional instrument covers four domains: physical health, psychological well-being, social relationships, and environment.
Higher scores within each domain reflect a more positive self-reported quality of life, meaning a better outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Incidence of Treatment-Emergent Adverse Events
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The incidence and severity of adverse events will be assessed throughout the study period, from baseline to the 4-week follow-up, to evaluate treatment safety and tolerability.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in Patient Health Questionnaire-9 (PHQ-9) Total Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Current depressive symptomatology will be quantified using the Patient Health Questionnaire-9 (PHQ-9).
It contains nine items, each rated on a scale from 0 to 3, yielding an aggregate score ranging from 0 to 27.
Elevated scores reflect a more severe depressive burden.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Baseline Credibility/Expectancy Questionnaire (CEQ) Score
時間枠：Baseline before the first stimulation session
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Participants' perceptions of the credibility of the intervention and their expectations regarding treatment benefit will be assessed using an adapted version of the Credibility/Expectancy Questionnaire (CEQ).
Higher scores indicate greater perceived credibility and higher expectations for treatment benefit, which represents a more positive expectancy.
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Baseline before the first stimulation session
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Change in the Positive and Negative Syndrome Scale (PANSS) Total Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Broader psychopathological status will be assessed using the 30-item Positive and Negative Syndrome Scale (PANSS).
Each of the 30 items is rated on a 1 to 7 ordinal scale, yielding a total score ranging from a minimum of 30 to a maximum of 210.
Higher scores denote a more severe psychopathological profile, meaning a worse outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in Resting-State Functional Connectivity (rs-fMRI)
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Exploratory analyses will investigate treatment-related neural changes using resting-state functional MRI (rs-fMRI).
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in Go/No-Go Task Accuracy
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Response inhibition will be evaluated with the computerized Go/No-Go paradigm.
The derived index reported here is overall accuracy, calculated as the percentage of correct responses.
Higher accuracy percentages indicate better response inhibition and cognitive control, meaning a better outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in Generalized Anxiety Disorder-7 (GAD-7) Total Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Anxiety over the preceding two weeks will be indexed by the Generalized Anxiety Disorder-7 scale (GAD-7).
It comprises seven items, each scored from 0 to 3, which are summed to a maximum total score of 21.
Higher totals denote greater anxiety severity.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in Pittsburgh Sleep Quality Index (PSQI) Global Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Sleep disturbance will be quantified with the Pittsburgh Sleep Quality Index (PSQI).
It is a 19-item self-report measure that generates a composite global score ranging from 0 to 21.
Higher values indicate worse sleep quality.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in Stroop Color-Word Task Interference Effect
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Conflict processing and cognitive control will be evaluated using the Stroop color-word task.
The primary metric evaluated is the Stroop interference effect, calculated based on the differences in reaction times between congruent and incongruent trials.
A lower interference effect score indicates better conflict processing and cognitive control, meaning a better outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in the Positive and Negative Syndrome Scale Positive Symptom Subscale Score
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The positive symptom subscale of the 30-item Positive and Negative Syndrome Scale (PANSS) will be evaluated to assess broader psychopathological status.
Clinician-assigned ratings for the items in this subscale are each anchored on a 1 to 7 ordinal scale.
Higher scores denote a more severe positive symptom profile, meaning a worse outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in White Matter Structural Connectivity via Diffusion Tensor Imaging (DTI)
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Exploratory analyses will investigate treatment-related neural changes using diffusion tensor imaging (DTI).
Changes in white matter structural connectivity will be evaluated to assess neural target engagement.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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Change in the Apathy Evaluation Scale Total Scor
時間枠：Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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The Apathy Evaluation Scale (AES-S) is a self-rated measure used to evaluate apathy.
The scale consists of 18 items that probe the cognitive, affective, and behavioral dimensions of apathetic experiences over the preceding four weeks.
Responses are summed to yield a total score ranging from 0 to 72.
Higher scores indicate more severe apathy, meaning a worse outcome.
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Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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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。
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 (実際)
2026年6月30日
一次修了 (推定)
2027年12月30日
研究の完了 (推定)
2027年12月30日
試験登録日
最初に提出
2026年6月8日
QC基準を満たした最初の提出物
2026年6月15日
最初の投稿 (実際)
2026年6月22日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月21日
QC基準を満たした最後の更新が送信されました
2026年8月19日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- ShanghaiPudong
個々の参加者データ (IPD) の計画
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いいえ
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