Efficacy and Safety of Individualized Sequential Accelerated Theta Burst Stimulation in Improving Cognitive Function in Schizophrenia
1 septembre 2026 mis à jour par: 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
Aperçu de l'étude
Statut
Pas encore de recrutement
Les conditions
Type d'étude
Interventionnel
Inscription (Estimé)
60
Phase
- N'est pas applicable
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Xingjie Peng, MD
- Numéro de téléphone: +86 151 1113 0170
- E-mail: 992348023@qq.com
Sauvegarde des contacts de l'étude
- Nom: Renrong Wu, MD
- Numéro de téléphone: +86 158 7417 9855
- E-mail: wurenrong@csu.edu.cn
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
Accepte les volontaires sains
Non
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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.
|
|
Comparateur factice: 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
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests
Délai: 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)
Délai: 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)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change in Psychotic Symptom Severity as Measured by the Positive and Negative Syndrome Scale (PANSS) Total Score
Délai: 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
Délai: 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
Délai: 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.
|
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)
Délai: 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
Délai: 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
Délai: 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)
|
|
Incidence of Adverse Events Related to SD-aTBS
Délai: 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)
Délai: 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
Délai: 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)
|
|
Change in P300 Event-Related Potential Amplitude
Délai: 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)
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Renrong Wu, Second Xiangya Hospital of Central South University
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Estimé)
30 septembre 2026
Achèvement primaire (Estimé)
30 septembre 2028
Achèvement de l'étude (Estimé)
30 septembre 2028
Dates d'inscription aux études
Première soumission
27 août 2026
Première soumission répondant aux critères de contrôle qualité
1 septembre 2026
Première publication (Réel)
8 septembre 2026
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
8 septembre 2026
Dernière mise à jour soumise répondant aux critères de contrôle qualité
1 septembre 2026
Dernière vérification
1 août 2026
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- LYG20260143
- 82325020 (Autre subvention/numéro de financement: National Natural Science Foundation of China)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
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
Délai de partage IPD
After publication
Critères d'accès au partage IPD
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.
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .