Cardiac Autonomic and Anxiety Regulation Via Closed-loop nEurofeedback in Recurrent Pregnancy Loss
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorShenyang Medical College
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
(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;
Disqualifiers
(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;
Trial design
Design model
Parallel
Treatments tested in this trial
Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback)
DeviceThis device-based intervention delivers fNIRS-BCI online closed-loop neurofeedback targeting the right dorsolateral prefrontal cortex (right DLPFC) with slow-wave acoustic cueing. Participants complete a 3-day adaptation phase followed by 3 weeks of formal training (15 weekday visits; about 20 minutes per visit). Each visit includes 20 blocks (60 seconds per block: 20 seconds rest + 40 seconds slow-wave acoustic cueing with a \~60 dB, 1 Hz sinusoidally amplitude-modulated pure tone). During each cueing period, real-time right DLPFC HbO activity estimated from fNIRS is displayed as a visual activation bar, and 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 mechanistic measures.
Right DLPFC fNIRS-BCI neurofeedback (sham feedback)
DeviceThis device-based sham intervention uses the same fNIRS-BCI neurofeedback interface, slow-wave acoustic cueing, and training schedule as the real-feedback arm. Participants complete a 3-day adaptation phase followed by 3 weeks of formal training (15 weekday visits; about 20 minutes per visit) using 20 blocks per visit (60 seconds per block: 20 seconds rest + 40 seconds slow-wave acoustic cueing with a \~60 dB, 1 Hz sinusoidally amplitude-modulated pure tone). fNIRS is recorded in all visits; ECG is recorded on the first formal training day only for HR/HRV measures. The displayed activation bar and concealed threshold line are configured to substantially weaken effective coupling to the participant's instantaneous neural activity (threshold setting: T = -1; approximating p = 0.31), making reliable volitional control unlikely while preserving blinding.
Treatment groups
62 Participants
are divided into 2 treatment groupsGroup A: a real-feedback intervention groupActive comparator 1 intervention
Group B: a sham-feedback control groupSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
the between-group difference in treatment response
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.
Time frame
Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.Secondary outcomes
1
Between-group difference in remission rate.
Remission will be defined as HAMA total score less than 8 together with a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved).
Time frame
Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.2
Between-group difference in continuous HAMA scores.
Anxiety severity will be measured using the Hamilton Anxiety Rating Scale (HAMA; 14 items, each scored 0-4; total score range 0-56; higher scores indicate greater anxiety severity). HAMA total score will be analysed as a continuous outcome to evaluate group, time, and group-by-time effects.
Time frame
Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.3
Between-group difference in downregulation of right DLPFC HbO activation.
During the slow-wave acoustic cueing-assisted neurofeedback task, fNIRS will be used to quantify participants ability to volitionally downregulate HbO activation in the right dorsolateral prefrontal cortex, and differences between groups will be compared.
Time frame
Day 4 after randomisation (first formal training day).4
Between-group difference in interhemispheric synchronisation within the DLPFC.
During the slow-wave acoustic cueing-assisted neurofeedback task, wavelet transform coherence (WTC) will be used to estimate the time-frequency coherence distribution between homologous left and right DLPFC channels as an index of interhemispheric synchrony and functional coupling. WTC values will be Fisher z-transformed and averaged within the target frequency band 0.01-0.05 Hz and within the task-relevant time window to derive an individual-level synchronisation metric for between-group comparison.
Time frame
Day 4 after randomisation (first formal training day).Other outcomes
1
The indirect effect of group assignment (real neurofeedback vs sham feedback) on HR change through change in right DLPFC activation.
Time frame
Day 4 after randomisation (first formal training day).2
The indirect effect of group assignment on 3-month anxiety improvement through change in right DLPFC activation
Time frame
Day 4 after randomisation (first formal training day) and 3 months after Day 24.3
The indirect effect of group assignment on 3-month anxiety improvement through HR change
Time frame
Day 4 after randomisation (first formal training day) and 3 months after Day 24.4
Model performance metrics
Operational performance of the online neurofeedback pipeline will be quantified, including mean per-frame total processing time (computation plus rendering) and frame-drop rate, as objective indicators of system stability and usability.
Time frame
Day 4 after randomisation (first formal training day).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov