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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
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.
干预措施: Sequential Dual-Site Accelerated Theta Burst Stimulation (SD-aTBS) (Device)
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.
干预措施: Sham Sequential Dual-Site Accelerated Theta Burst Stimulation (Device)
结局指标
主要结局
Change in Global Cognitive Function as Measured by the Mean Composite T-Score Derived from 14 Neuropsychological Tests
时间窗: 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.
Change in Synaptic Density as Measured by [18F]SV2A-PET Standardized Uptake Value Ratio (SUVR)
时间窗: 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.
次要结局
- 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))
- Change in Peripheral Blood Biomarker Concentrations(Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3))
- Incidence of Adverse Events Related to SD-aTBS(Daily during the 10-day intervention period)
- Change in 40 Hz Auditory Steady-State Response (ASSR)(Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3))
- Change in Mismatch Negativity (MMN) Amplitude(Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3))
- Change in P300 Event-Related Potential Amplitude(Baseline, immediately after the intervention (Day 10), and at Follow-up (Day 40 ± 3))
研究者
Renrong Wu
Professor
Central South University