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dACC-Targeted Temporal Interference for Negative and Cognitive Symptoms in Schizophrenia

2026년 8월 19일 업데이트: 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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

74

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 중국
      • Shanghai, 중국
        • 모병
        • Shanghai Pudong New Area Mental Health Center
        • 연락하다:
          • Wufan
          • 전화번호: 021-68306699*1222

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

Inclusion Criteria:

  • All of the following criteria must be satisfied for enrolment:

    1. 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);
    2. Age between 18 and 65 years, regardless of sex, with completion of at least junior secondary education and the capacity to undergo neurocognitive testing;
    3. 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;
    4. 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;
    5. 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;
    6. 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:

    1. 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;
    2. Current or past substance use disorder, encompassing problematic consumption of alcohol or illicit substances;
    3. A documented seizure disorder or marked electroencephalographic abnormalities, particularly epileptiform activity;
    4. Evidence of structural brain pathology, including organic lesions, prior traumatic brain injury, or previous neurosurgical intervention;
    5. Presence of ferromagnetic implants or any other contraindication to MRI or tTIS exposure, including intracranial metallic clips, implanted cardiac devices, or cochlear implants;
    6. Current use of glucocorticoids or other pharmacological agents known to meaningfully alter cortical excitability;
    7. 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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 더블

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
장치: Temporal Interference Stimulation
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.
가짜 비교기: 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.
장치: Sham Temporal Interference Stimulation
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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Change in the Positive and Negative Syndrome Scale Negative Symptom Subscale Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up

2차 결과 측정

결과 측정
측정값 설명
기간
Change in the Brief Assessment of Cognition in Schizophrenia Composite Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in the Scale for the Assessment of Negative Symptoms Total Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in the Temporal Experience of Pleasure Scale Total Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in the Personal and Social Performance Scale Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in the World Health Organization Quality of Life-BREF Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Incidence of Treatment-Emergent Adverse Events
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in Patient Health Questionnaire-9 (PHQ-9) Total Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Baseline Credibility/Expectancy Questionnaire (CEQ) Score
기간: Baseline before the first stimulation session
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.
Baseline before the first stimulation session
Change in the Positive and Negative Syndrome Scale (PANSS) Total Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in Resting-State Functional Connectivity (rs-fMRI)
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Exploratory analyses will investigate treatment-related neural changes using resting-state functional MRI (rs-fMRI).
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in Go/No-Go Task Accuracy
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in Generalized Anxiety Disorder-7 (GAD-7) Total Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in Pittsburgh Sleep Quality Index (PSQI) Global Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in Stroop Color-Word Task Interference Effect
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in the Positive and Negative Syndrome Scale Positive Symptom Subscale Score
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in White Matter Structural Connectivity via Diffusion Tensor Imaging (DTI)
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
Change in the Apathy Evaluation Scale Total Scor
기간: Baseline, immediately after the 2-week intervention, and at the 4-week follow-up
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.
Baseline, immediately after the 2-week intervention, and at the 4-week follow-up

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2026년 6월 30일

기본 완료 (추정된)

2027년 12월 30일

연구 완료 (추정된)

2027년 12월 30일

연구 등록 날짜

최초 제출

2026년 6월 8일

QC 기준을 충족하는 최초 제출

2026년 6월 15일

처음 게시됨 (실제)

2026년 6월 22일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 8월 21일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 8월 19일

마지막으로 확인됨

2026년 6월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

  • ShanghaiPudong

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

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아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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