Recurrent Pregnancy LossCARE-RPLNCT07325370
Cardiac Autonomic and Anxiety Regulation Via Closed-loop nEurofeedback in Recurrent Pregnancy Loss
A study testing Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback) in people with Recurrent Pregnancy Loss and Anxiety, run by Shenyang Medical College at 2 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Recurrent Pregnancy Loss, Anxiety
- What is being tested?
- Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 2 sitesChina
- Study dates
- 29 Dec 2025to 30 Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- (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.
Who cannot join
- (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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
The Second Affiliated Hospital of Shenyang Medical College
Shenyang, Liaoning, 110001
Xiu-Ling Zhang, MD, 86-024-31236568, 2238501927@qq.com
- Recruiting
Central Hospital Affiliated to Shenyang Medical College
Shenyang, Liaoning, 110024
Fei Meng, MD, mengfei665@sohu.com
Fei Meng, MD
About this study
Official title: 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
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:
Read more
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
Read the detailed description
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.
- Conditions
- Recurrent Pregnancy Loss, Anxiety
- Being tested
- Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback), Right DLPFC fNIRS-BCI neurofeedback (sham feedback)
- Keywords
- Recurrent pregnancy loss, Anxiety disorders, Right dorsolateral prefrontal cortex, Functional near-infrared spectroscopy, Brain-computer interface, Closed-loop neurofeedback, Cardiac autonomic function, Brain-heart coupling
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback)Device
This 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)Device
This 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.
| Study group | Role | What they receive |
|---|---|---|
| a real-feedback intervention group | Active comparator | 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. Receives: Device: Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback) |
| a sham-feedback control group | Sham comparator | 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. Receives: Device: Right DLPFC fNIRS-BCI neurofeedback (sham feedback) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.
Secondary outcomes (7)
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).
Measured: 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.
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.
Measured: 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.
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.
Measured: Day 4 after randomisation (first formal training day).
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.
Measured: Day 4 after randomisation (first formal training day).
Between-group difference in baseline-corrected heart-rate change.
During the slow-wave acoustic cueing-assisted neurofeedback task, baseline-corrected changes in heart rate (HR) will be compared between groups to evaluate between-group differences in acute cardiac autonomic responses.
Measured: Day 4 after randomisation (first formal training day).
Between-group difference in HRV spectral power at 0.0167 Hz.
Using wavelet-based time-frequency analysis, the investigators will compare between-group differences in HRV spectral power at 0.0167 Hz (corresponding to the 60-second cycle and within the very-low-frequency range of HRV) to characterise autonomic rhythmic responses to the neurofeedback task and slow-wave rhythmic cueing.
Measured: Day 4 after randomisation (first formal training day).
Between-group difference in adverse events during the intervention period.
Specifically, the investigators will compare the overall proportion of participants experiencing at least one adverse event (AE) in the real neurofeedback group versus the sham-feedback group, and will additionally compare the occurrence of prespecified AE categories, including but not limited to mild dizziness or somnolence, transient bradycardia- or blood-pressure-related discomfort, and headache or nausea.
Measured: From Day 1 (start of adaptation training) through Day 24 (end of treatment).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2026
- Study start29 Dec 2025
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Pregnancy LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, sham-controlled, parallel-group, two-arm interventional study model with 1:1 allocation. Eligible women with recurrent pregnancy loss and comorbid anxiety will be assigned to real right DLPFC fNIRS-BCI online closed-loop neurofeedback or sham feedback. Both arms will use an identical training schedule and procedures: a 3-day adaptation phase followed by 3 weeks of formal training (15 sessions; one weekday session/day; \~20 min/session) using a block design (20 blocks/session; 60 s per block: 20 s rest + 40 s slow-wave acoustic cueing with a 1 Hz amplitude-modulated tone). fNIRS will be recorded in all sessions; ECG will be recorded only in session 1 for HR/HRV mechanistic outcomes. Outcomes will be assessed at baseline, end of treatment, and 3-month follow-up.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenyang Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lin Tao, Shenyang Medical College
- Investigators
- Lin Tao, MM, Principal investigator, Shenyang Medical CollegeYun-En Liu, MD, Study chair, Shenyang Medical CollegeFei Meng, MD, Study director, Central Hospital Affiliated to Shenyang Medical Collage
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07325370
- Sponsor's protocol ID
- CARE-RPL
- Acronym
- CARE-RPL
- Status last verified
- Dec 2025
- First submitted
- 22 Dec 2025
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07325370
- Acronym / sponsor ID
- CARE-RPL / CARE-RPL
- Conditions
- Recurrent Pregnancy Loss, Anxiety
- Keywords
- Recurrent pregnancy loss, Anxiety disorders, Right dorsolateral prefrontal cortex, Functional near-infrared spectroscopy, Brain-computer interface, Closed-loop neurofeedback, Cardiac autonomic function, Brain-heart coupling
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Shenyang Medical CollegeUniversity, hospital or other
- Study start
- 29 Dec 2025 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 30 Oct 2026 (estimated)
- First posted
- 8 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, sham-controlled, parallel-group, two-arm interventional study model with 1:1 allocation. Eligible women with recurrent pregnancy loss and comorbid anxiety will be assigned to real right DLPFC fNIRS-BCI online closed-loop neurofeedback or sham feedback. Both arms will use an identical training schedule and procedures: a 3-day adaptation phase followed by 3 weeks of formal training (15 sessions; one weekday session/day; ~20 min/session) using a block design (20 blocks/session; 60 s per block: 20 s rest + 40 s slow-wave acoustic cueing with a 1 Hz amplitude-modulated tone). fNIRS will be recorded in all sessions; ECG will be recorded only in session 1 for HR/HRV mechanistic outcomes. Outcomes will be assessed at baseline, end of treatment, and 3-month follow-up.
| Arm | Type | Receives |
|---|---|---|
| a real-feedback intervention group | Active comparator | Device: Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback)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. |
| a sham-feedback control group | Sham comparator | Device: Right DLPFC fNIRS-BCI neurofeedback (sham feedback)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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- (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.
Key exclusion criteria (5 listed)
- (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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback)This 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. | Device | a real-feedback intervention group |
| Right DLPFC fNIRS-BCI neurofeedback (sham feedback)This 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. | Device | a sham-feedback control group |
Primary outcome
the between-group difference in treatment response
Time frame: 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.
7 secondary outcomes
Between-group difference in remission rate.
Time frame: 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.
Time frame: 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.
Time frame: Day 4 after randomisation (first formal training day).
Between-group difference in interhemispheric synchronisation within the DLPFC.
Time frame: Day 4 after randomisation (first formal training day).
Between-group difference in baseline-corrected heart-rate change.
Time frame: Day 4 after randomisation (first formal training day).
Between-group difference in HRV spectral power at 0.0167 Hz.
Time frame: Day 4 after randomisation (first formal training day).
Between-group difference in adverse events during the intervention period.
Time frame: From Day 1 (start of adaptation training) through Day 24 (end of treatment).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lin Tao, MM principal investigator
Shenyang Medical College
Yun-En Liu, MD study chair
Shenyang Medical College
Fei Meng, MD study director
Central Hospital Affiliated to Shenyang Medical Collage
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Right DLPFC fNIRS-BCI closed-loop neurofeedback (real feedback) in people with Recurrent Pregnancy Loss and Anxiety, run by Shenyang Medical College at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fei Meng, MD (86-024-85715635, mengfei665@sohu.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the between-group difference in treatment response (time frame: Day 0 (baseline, pre-intervention); Day 24 (end of treatment, within 1 hour after completion of training); 3 months after Day 24.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026; AzTrials last refreshed its copy on 7 Nov 2026.