Efficacy and Safety of Individualized Sequential Accelerated Theta Burst Stimulation in Improving Cognitive Function in Schizophrenia
1. september 2026 oppdatert av: 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
Studieoversikt
Status
Har ikke rekruttert ennå
Studietype
Intervensjonell
Registrering (Antatt)
60
Fase
- Ikke aktuelt
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Xingjie Peng, MD
- Telefonnummer: +86 151 1113 0170
- E-post: 992348023@qq.com
Studer Kontakt Backup
- Navn: Renrong Wu, MD
- Telefonnummer: +86 158 7417 9855
- E-post: wurenrong@csu.edu.cn
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
Tar imot friske frivillige
Nei
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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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Sham-komparator: 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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests
Tidsramme: 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)
Tidsramme: 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.
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Baseline and Follow-up (Day 40 ± 3)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in Psychotic Symptom Severity as Measured by the Positive and Negative Syndrome Scale (PANSS) Total Score
Tidsramme: 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.
|
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
Tidsramme: 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)
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Change in Treatment-Emergent Adverse Event Severity as Measured by the Treatment Emergent Symptom Scale (TESS) Total Score
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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.
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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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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.
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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
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Hovedetterforsker: Renrong Wu, Second Xiangya Hospital of Central South University
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Antatt)
30. september 2026
Primær fullføring (Antatt)
30. september 2028
Studiet fullført (Antatt)
30. september 2028
Datoer for studieregistrering
Først innsendt
27. august 2026
Først innsendt som oppfylte QC-kriteriene
1. september 2026
Først lagt ut (Faktiske)
8. september 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
8. september 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
1. september 2026
Sist bekreftet
1. august 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- LYG20260143
- 82325020 (Annet stipend/finansieringsnummer: National Natural Science Foundation of China)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
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-delingstidsramme
After publication
Tilgangskriterier for IPD-deling
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-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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