Right Dorsolateral Prefrontal Cortex-Targeted fNIRS-BCI Closed-loop Neurofeedback for Anxiety Relief and Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss: a Randomized, Sham-controlled Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 62
- 试验地点
- 2
- 主要终点
- the between-group difference in treatment response
研究概览
简要总结
The goal of this clinical trial is to learn whether right dorsolateral prefrontal cortex (right DLPFC)-targeted fNIRS-BCI online closed-loop neurofeedback, delivered with slow-wave acoustic cueing, can reduce anxiety symptoms and improve cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety (women aged 18-45 years, right-handed, currently not pregnant or in a missed miscarriage state).
The main questions it aims to answer are:
Does real neurofeedback increase the proportion of participants who achieve an anxiety treatment response (defined as ≥50% reduction in Hamilton Anxiety Rating Scale [HAMA] total score from baseline) compared with sham feedback, at end of treatment and at 3-month follow-up? Is the intervention safe and well tolerated, as reflected by between-group differences in adverse events during the training period? Do brain and autonomic measures show between-group differences during the first formal session, including right DLPFC HbO downregulation, interhemispheric DLPFC synchronisation, heart rate (HR), and heart rate variability (HRV) indices? Researchers will compare real right DLPFC neurofeedback to sham feedback (identical procedures and displays but weakened coupling to real-time neural activity) to see if real neurofeedback improves anxiety outcomes and brain-heart autonomic regulation.
Participants will:
Complete screening, baseline clinical assessments, and physical examination Be randomly assigned (1:1) to real neurofeedback or sham feedback Complete 3 days of adaptation training followed by 3 weeks of training (15 sessions; one weekday session per day; ~20 minutes each) using a block design with slow-wave acoustic cueing (1 Hz amplitude-modulated tone; 20 s rest + 40 s cueing per block; 20 blocks/session) Undergo fNIRS recording in all sessions, with ECG recorded in session 1 only (for HR/HRV analyses) Receive matched, guideline-informed cognitive-behavioural therapy (CBT) during the intervention period Complete anxiety-related assessments at baseline, ~1 hour after the final session, and 3 months after treatment, with adverse events monitored throughout the intervention period
详细描述
This study is a mechanistically informed, prospective, randomized, sham-controlled, parallel-group clinical trial designed to evaluate whether right dorsolateral prefrontal cortex (right DLPFC)-targeted fNIRS-BCI online closed-loop neurofeedback, delivered with slow-wave acoustic cueing, improves anxiety symptoms and cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety. Participants who meet eligibility criteria will be randomized in a 1:1 ratio to either real neurofeedback or sham feedback, with identical visit structure and procedures across groups.
The intervention will use an online neurofeedback pipeline to estimate right DLPFC activation from fNIRS signals in real time and present a visual activation bar to guide volitional downregulation of the target region during slow-wave acoustic cueing. The sham condition will use the same interface, cueing, and workflow but with feedback parameters configured to substantially weaken effective coupling between the displayed feedback and the participant's instantaneous neural state. fNIRS will be recorded across all training sessions, and ECG will be recorded during the first formal training session only to quantify heart rate and heart rate variability and to support mechanistic analyses of short-term brain-heart coupling during the task.
Clinical outcomes will focus on changes in anxiety severity over time, assessed at baseline, at the end of treatment, and at 3-month follow-up. Neurophysiological endpoints will be derived from the first formal session to characterize task-related right DLPFC downregulation, interhemispheric DLPFC synchrony, and cardiac autonomic responses during the neurofeedback task. Safety and tolerability will be evaluated by comparing the incidence and profile of adverse events between groups throughout the intervention period. In addition, both groups will receive matched, guideline-informed cognitive-behavioural therapy (CBT) during the intervention period as background standard care, and any clinically indicated psychotropic medication use during follow-up will be documented for analytic control.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Masking (blinding) will be implemented at multiple levels. Participants will be blinded to group assignment, and both groups will receive identical slow-wave acoustic cueing, session structure, instructions, and an indistinguishable on-screen feedback interface with the numerical threshold concealed. Outcome assessors (clinical raters) and data analysts/statisticians will remain blinded throughout data collection and primary analyses. Only the session operator responsible for loading group-specific neurofeedback parameters will be unblinded, and will not participate in outcome assessments or statistical analyses. Emergency unblinding will be permitted only when clinically necessary for participant safety and will be documented according to prespecified procedures.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •(i) Women aged 18-45 years, right-handed;
- •(ii) Diagnosis of recurrent pregnancy loss (RPL), defined as ≥2 consecutive spontaneous pregnancy losses occurring before 28 weeks of gestation;
- •(iii) Not currently pregnant, or currently in a missed miscarriage state;
- •(iv) Meet DSM-5 diagnostic criteria for an anxiety disorder, with at least moderate severity, defined as Clinical Global Impression-Severity (CGI-S) ≥4;
- •(v) Hamilton Anxiety Rating Scale (HAMA) ≥16, with 17-item Hamilton Depression Rating Scale (HAMD-17) <17, to ensure anxiety is the predominant affective disturbance.
排除标准
- •(i) Markedly unstable blood pressure (systolic BP >180 mmHg or <90 mmHg);
- •(ii) Clinically important comorbid organic diseases, including but not limited to hyperthyroidism, history of atrial fibrillation, sinus bradycardia, major neurological disorders, cerebrovascular disease, or severe pulmonary disease;
- •(iii) Significant suicide risk, judged by psychiatric assessment to be unsuitable for study participation;
- •(iv) Other severe psychiatric disorders, including substance use disorder, schizophrenia, delusional disorder, unspecified psychotic disorder, bipolar disorder, or delirium;
- •(v) Use of any oral antidepressant, anxiolytic, or antipsychotic medication within the past 4 weeks, or fluoxetine within the past 6 weeks, or any long-acting injectable antipsychotic within the past 3 months.
研究组 & 干预措施
a real-feedback intervention group
Participants will receive right DLPFC targeted fNIRS-BCI online closed-loop neurofeedback delivered with slow-wave acoustic cueing. Training includes a 3-day adaptation phase followed by 3 weeks of formal training (15 weekday visits; about 20 minutes per visit) using a block design (20 blocks per visit; 60 seconds per block: 20 seconds rest + 40 seconds slow-wave acoustic cueing with a 1 Hz sinusoidally amplitude-modulated pure tone at about 60 dB). During each cueing period, real-time right DLPFC activation estimated from fNIRS is displayed as a visual activation bar; participants apply volitional strategies to downregulate activity below a concealed threshold line (T = -3.3; approximating p = 0.001). fNIRS is recorded in all visits; ECG is recorded on the first formal training day only for HR/HRV measures.
干预措施: Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback) (Device)
a sham-feedback control group
Participants will receive sham fNIRS-BCI neurofeedback targeting the right DLPFC under procedures identical in appearance and schedule to the real-feedback arm, including the same slow-wave acoustic cueing and block design (20 blocks per visit; 60 seconds per block: 20 seconds rest + 40 seconds cueing with a 1 Hz sinusoidally amplitude-modulated pure tone at about 60 dB). fNIRS is recorded in all visits; ECG is recorded on the first formal training day only for HR/HRV measures. The on-screen interface and concealed threshold line are identical; however, feedback parameters are configured to substantially weaken effective coupling between the displayed activation bar and the participant's instantaneous neural activity (T = -1; approximating p = 0.31), making stable volitional control unlikely while preserving blinding.
干预措施: Right DLPFC fNIRS-BCI neurofeedback (sham feedback) (Device)
结局指标
主要结局
the between-group difference in treatment response
时间窗: Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.
The investigators will compare the overall proportion of participants achieving response in the real neurofeedback group versus the sham-feedback group across the post-treatment follow-up period, defined by two timepoints: end of treatment and 3-month follow-up. Anxiety symptoms will be assessed using the Hamilton Anxiety Rating Scale (HAMA; ; 14 items, each scored 0-4; total score range 0-56; higher scores indicate greater anxiety severity), and treatment response will be defined a priori as a reduction of at least 50% in total HAMA score from baseline.
次要结局
- Between-group difference in remission rate.(Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.)
- Between-group difference in continuous HAMA scores.(Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.)
- Between-group difference in downregulation of right DLPFC HbO activation.(Day 4 after randomisation (first formal training day).)
- Between-group difference in interhemispheric synchronisation within the DLPFC.(Day 4 after randomisation (first formal training day).)
- Between-group difference in baseline-corrected heart-rate change.(Day 4 after randomisation (first formal training day).)
- Between-group difference in HRV spectral power at 0.0167 Hz.(Day 4 after randomisation (first formal training day).)
- Between-group difference in adverse events during the intervention period.(From Day 1 (start of adaptation training) through Day 24 (end of treatment).)
研究者
Lin Tao
Assoc.Prof.
Shenyang Medical College