Efficacy and Safety of Individualized Sequential Accelerated Theta Burst Stimulation in Improving Cognitive Function in Schizophrenia

NCT07806877 | Not Yet Recruiting DMC

• 2 other identifiers: LYG2026014382325020
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Schizophrenia / Schizoaffective Disorder; TMS; PET / MR; Cognitive

Keywords

Schizophrenia; Cognitive dysfunction; TMS; SV2A-PET

Outcome Measures

Primary Outcomes (2)

• Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests

  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)

  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)

Secondary Outcomes (10)

• Change in Psychotic Symptom Severity as Measured by the Positive and Negative Syndrome Scale (PANSS) Total Score

  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

  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

  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)

  Baseline, post-intervention, and Follow-up (Day 40 ± 3)

• Change in Resting-State EEG Spectral Power

  Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3)

Study Arms (2)

active SD-TBS group

EXPERIMENTAL

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.

Device: Sequential Dual-Site Accelerated Theta Burst Stimulation (SD-aTBS)

sham SD-TBS group

SHAM COMPARATOR

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.

Device: Sham Sequential Dual-Site Accelerated Theta Burst Stimulation

Interventions

Sham Sequential Dual-Site Accelerated Theta Burst Stimulation DEVICE

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

sham SD-TBS group

Sequential Dual-Site Accelerated Theta Burst Stimulation (SD-aTBS) DEVICE

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.

active SD-TBS group

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Central South University: lead

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Officials

• Renrong Wu

  Second Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingjie Peng, MD

CONTACT

+86 151 1113 0170; 992348023@qq.com

Renrong Wu, MD

CONTACT

+86 158 7417 9855; wurenrong@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomly assigned in a 1:1 ratio to receive either real SD-aTBS or sham stimulation, in a parallel-group design

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 8, 2026
• Study Start: September 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: September 8, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After publication
• Access Criteria: 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.