Recurrent Pregnancy Loss(RPL)NCT07233278
High-Intensity, Low-Frequency Periodic rTMS Over the Right Dorsolateral Prefrontal Cortex on Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss and Anxiety
A study testing Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles in people with Recurrent Pregnancy Loss(RPL) and Anxiety, run by Shenyang Medical College at 3 sites in China.
Trial summary
The goal of this clinical trial is to determine whether high-intensity, low-frequency periodic repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) can modulate cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Recurrent Pregnancy Loss(RPL), Anxiety
- What is being tested?
- Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 3 sitesChina
- Study dates
- 19 Nov 2025to 30 Dec 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) Female, aged 18-45 years, and right-handed;
- (ii) Diagnosed with recurrent pregnancy loss (RPL), defined as two or more consecutive spontaneous miscarriages occurring before 28 weeks of gestation;
- (iii) Not currently pregnant or in a state of missed miscarriage;
- (iv) Meeting the DSM-5 diagnostic criteria for GAD, with a HAMA score of at least 16, a CGI-S score of at least 4, and a HAMD-17 score of no more than 17.
Who cannot join
- (i) Contraindications to transcranial magnetic stimulation (TMS), such as metallic implants or a history of epilepsy;
- (ii) Unstable blood pressure (systolic >180 mmHg or <90 mmHg);
- (iii) Coexisting major organic disorders, including hyperthyroidism, atrial fibrillation, valvular heart disease, sinus bradycardia, neurological diseases, cerebrovascular disease, or pulmonary disorders;
- (iv) Significant suicide risk;
- (v) Other current major psychiatric disorders, including substance use disorder, schizophrenia, delusional disorder, unspecified psychotic disorder, bipolar disorder, or delirium. To preserve diagnostic homogeneity of the study sample, participants whose current primary diagnosis is another anxiety-related disorder will also be excluded, including panic disorder, social anxiety disorder, separation anxiety disorder, specific phobia, obsessive-compulsive and related disorders, and trauma- and stressor-related disorders; Current use of psychotropic medication at screening, or continuous use within the 4 weeks before screening of antidepressants, anxiolytics, antipsychotics, mood stabilizers, or sedative-hypnotics, in order to minimize hemodynamic confounding.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 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, 86-024-85715635, mengfei665@sohu.com
- Recruiting
242 Hospital Affiliated to Shenyang Medical College
Shenyang, Liaoning, 110086
Lu-Wei Zhang, MD, 86-13904005901, 2907311795@qq.com
About this study
Official title: High-intensity, Low-frequency Periodic rTMS Over the Right Dorsolateral Prefrontal Cortex for Acute Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss and Generalized Anxiety Disorder: a Randomized, Sham-controlled Mechanistic Trial (NEURO-CARD-rTMS-2)
The goal of this clinical trial is to determine whether high-intensity, low-frequency periodic repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) can modulate cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety. The main questions it aims to answer are:
Does 120% resting motor threshold (RMT) rhythmic low-frequency rTMS reduce heart rate during stimulation time windows compared with sham stimulation?
Read more
Does 120% RMT rTMS alter heart-rate-variability (HRV) spectral power at the target frequency (0.0167 Hz) compared with sham stimulation?
Researchers will compare active rTMS with sham rTMS to determine whether the active intervention produces measurable changes in cardiac autonomic activity.
Participants will:
Undergo a single session of rTMS or sham stimulation consisting of 20 consecutive stimulation time windows (each 60 seconds: 40 seconds of 1-Hz stimulation plus 20 seconds of rest) targeting the right DLPFC;
Have continuous electrocardiography (ECG) recordings collected during the entire stimulation session;
Complete clinical and psychiatric assessments before participation.
Read the detailed description
For this protocol, recurrent pregnancy loss (RPL) was defined as two or more consecutive spontaneous miscarriages before 28 weeks of gestation. RPL affects approximately 2-5% of reproductive-age couples worldwide and imposes a substantial clinical and emotional burden. Beyond its implications for reproductive health, RPL is increasingly recognized as a condition associated with systemic consequences, including heightened anxiety, altered autonomic nervous system function, and increased long-term cardiovascular risk.
Emerging evidence suggests that in women with RPL and comorbid anxiety, chronic psychological stress may lead to dysregulation of the autonomic nervous system, characterized by increased sympathetic tone, reduced vagal activity, elevated resting heart rate, and decreased heart rate variability (HRV). These alterations may create a maladaptive feedback loop that reinforces emotional distress, autonomic imbalance, and reproductive vulnerability.
To address this issue, this randomized, sham-controlled, proof-of-concept clinical trial will investigate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right dorsolateral prefrontal cortex (DLPFC)-a region critically involved in emotion regulation and autonomic control-can modulate cardiac autonomic function in women with RPL and anxiety.
The intervention protocol is based on findings from a prior dose-finding study (NEURO-CARD-rTMS-1), which indicated that stimulation at 120% of resting motor threshold (RMT) produced significant reductions in heart rate without compromising tolerability. Building on this, the current trial (NEURO-CARD-rTMS-2) will apply 1-Hz rhythmic rTMS at 120% RMT over the right DLPFC, delivered in 20 consecutive stimulation windows (each 60 seconds long: 40 seconds of stimulation followed by 20 seconds of rest). This stimulation paradigm aligns with the very-low-frequency (VLF) band of HRV (~0.0167 Hz), enabling frequency-specific entrainment analysis.
The primary endpoint will be the difference in baseline-corrected mean heart rate during the stimulation time windows between the active and sham groups. Secondary endpoints include changes in HRV spectral power at 0.0167 Hz and brain-heart coupling (BHC), defined as the correlation between heart rate and spectral power at this frequency. Safety outcomes will be monitored throughout the procedure.
All electrocardiographic (ECG) data will be recorded continuously at 1000 Hz using a wireless Bluetooth system. Participants will undergo standardized psychiatric assessments based on DSM-5 criteria, and key demographic and clinical variables (e.g., BMI, blood pressure, medication use, number and cause of miscarriages) will be collected for covariate analysis.
This trial aims to provide initial mechanistic evidence for the feasibility and physiological efficacy of right DLPFC-targeted neuromodulation in improving autonomic regulation in a high-risk, psychologically sensitive population. If successful, the findings will support the development of non-invasive, brain-based interventions to improve both reproductive and cardiovascular outcomes in women with RPL and anxiety.
- Conditions
- Recurrent Pregnancy Loss(RPL), Anxiety
- Being tested
- Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles, Sham rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles
- Keywords
- Recurrent pregnancy loss, Anxiety, Dorsolateral Prefrontal Cortex, Cardiac Autonomic Regulation, repetitive transcranial magnetic stimulation
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cyclesDevice
Participants assigned to the active rTMS group will receive rhythmic low-frequency repetitive transcranial magnetic stimulation applied over the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the intervention consists of 20 consecutive stimulation cycles, each comprising 40 seconds of 1 Hz stimulation followed by a 20-second inter-cycle interval, for a total of 60 seconds per cycle. The stimulation intensity is set at 120% of the individual resting motor threshold (RMT). A figure-of-eight coil will be positioned tangentially over the scalp at the targeted right DLPFC site. Electrocardiogram (ECG) signals will be recorded continuously throughout the session. After completion of the acute Stage 1 procedure and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants who enter Stage 2 will cont
Sham rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cyclesDevice
Participants assigned to the sham rTMS group will receive sham rhythmic low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the sham procedure matches the active condition in timing, coil position, and auditory and tactile experience, with 20 consecutive sham stimulation cycles, each comprising 40 seconds of simulated stimulation followed by a 20-second inter-cycle interval, for a total of 60 seconds per cycle. The coil will be held at a 45-degree angle to the scalp to minimize effective cortical stimulation while preserving the sensory characteristics of the procedure. Electrocardiogram (ECG) signals will be recorded continuously throughout the session. After completion of the acute Stage 1 procedure and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original ran
| Study group | Role | What they receive |
|---|---|---|
| real rTMS group | Active comparator | Participants in this arm will receive active repetitive transcranial magnetic stimulation (rTMS) delivered to the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the stimulation protocol consists of 20 consecutive cycles of low-frequency (1 Hz) rTMS at 120% of the resting motor threshold (RMT), with each cycle comprising 40 seconds of stimulation followed by 20 seconds of rest. The total stimulation duration is approximately 20 minutes. Real stimulation is applied with the figure-of-eight coil positioned tangentially to the scalp. After completion of Stage 1 and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants who enter Stage 2 will continue to receive active stimulation under the same fixed-parameter framework; no re-randomization will be performed. Receives: Device: Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles |
| sham rTMS group | Sham comparator | Participants in this arm will receive sham repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the stimulation protocol mimics the active condition in timing and coil placement but involves tilting the coil at a 45-degree angle to the scalp, significantly attenuating magnetic field penetration. This approach preserves the auditory and tactile sensations of stimulation without producing cortical effects. The procedure consists of 20 consecutive cycles of sham stimulation, each comprising 40 seconds of simulated stimulation followed by 20 seconds of rest, lasting approximately 20 minutes in total. After completion of Stage 1 and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants who enter Stage 2 will continue to receive sham stimu Receives: Device: Sham rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be the between-group difference in baseline-corrected mean heart rate, averaged across stimulation time windows.
Heart rate (HR) will be continuously recorded via ECG (1,000 Hz) during a single rTMS session comprising 20 stimulation cycles (each 60 s: 40 s stimulation at 1 Hz, then 20 s rest). For each cycle, a 50-s analysis window will be defined (-10 s to 0 s pre-stimulation baseline; 0 s to +40 s post-stimulation). Baseline-corrected mean HR for each cycle will be computed as the mean HR in the post-stimulation segment (0-40 s) minus the mean HR in the 10-s pre-stimulation baseline (-10-0 s). Per-participant values will then be averaged across the 20 stimulation time windows, and the primary endpoint will compare these averaged baseline-corrected means between the active and sham rTMS groups.
Measured: Session 1 (Day 1)
Secondary outcomes (5)
The between-group difference in heart rate variability (HRV) spectral power at the target frequency (0.0167 Hz), averaged across stimulation time windows.
HRV spectral power at the target frequency will be derived from R-R interval (RRI) series obtained from continuous ECG recorded at 1,000 Hz. Following resampling, linear detrending, and band-pass filtering, the RRI series will undergo wavelet-based time-frequency analysis. For each stimulation cycle, mean wavelet power within the target frequency band will be quantified over the corresponding analysis window. Window-level estimates will then be averaged across the 20 cycles to obtain a participant-level summary measure, which will be compared between the active and sham groups.
Measured: Session 1 (Day 1)
The strength of the linear correlation between baseline-corrected mean heart rate and spectral power at 0.0167 Hz, averaged across stimulation time windows, in the active rTMS group.
For each participant in the active rTMS group, the linear correlation (Pearson's r) between these two window-wise measures will be calculated across the 20 stimulation time windows.
Measured: Session 1 (Day 1)
The strength of the linear correlation between baseline-corrected mean heart rate and spectral power at 0.0167 Hz, averaged across stimulation time windows, in the sham rTMS group.
For each participant in the sham rTMS group, the linear correlation (Pearson's r) between these two window-wise measures will be calculated across the 20 stimulation time windows.
Measured: Session 1 (Day 1)
Incidence of mild adverse events during rTMS stimulation, including scalp discomfort at the stimulation site, facial muscle twitching, mild headache, and dizziness.
This outcome will capture the incidence (proportion of participants with ≥1 event) of prespecified mild adverse events during the rTMS session and the immediate 1-hour post-session observation period. Mild events include scalp discomfort at the stimulation site, facial muscle twitching, mild headache, and dizziness. Events will be solicited and recorded in real time by trained operators using a standardized checklist, with participant self-report. Vital signs (blood pressure and resting heart rate) will be reassessed at the end of the session. Events will be classified as mild if transient, self-limited, not requiring medical treatment, and not meeting serious adverse event criteria (e.g., syncope or seizure). Incidence will be summarized by group (active vs sham) for comparison.
Measured: Session 1 (Day 1)
Incidence of serious adverse events during rTMS stimulation, including syncope and seizures.
This outcome will quantify the incidence (proportion of participants with ≥1 event) of serious adverse events (SAEs) occurring during the rTMS session and the subsequent 1-hour observation period. SAEs will be defined per ICH-GCP criteria (events that are fatal, life-threatening, require inpatient hospitalization or prolong an existing hospitalization, result in persistent or significant disability/incapacity, or are otherwise medically important). Events of special interest include syncope and seizures. Trained operators will actively monitor and document SAEs in real time using standardized case-report forms, including onset time, duration, actions taken, outcome, and relatedness to the intervention. Any suspected SAE will trigger protocol-specified safety procedures (immediate termination of stimulation, vital-sign reassessment, medical evaluation, and referral as needed). Incidence will be summarized by group (active vs sham).
Measured: Session 1 (Day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2025
- Study start19 Nov 2025
- Primary completion22 Jul 2026
- Study completion30 Dec 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 Loss(RPL)Studies 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
- This study will use a parallel assignment interventional model. Participants will be randomly assigned in a 1:1 ratio to either the active rTMS group or the sham rTMS group.In Stage 1, each participant will receive a single-session intervention under their assigned condition. The intervention will be delivered in a controlled laboratory setting, and both groups will undergo identical procedures except for the presence or absence of effective magnetic stimulation. This design allows for between-group comparison of physiological responses and safety outcomes attributable to the intervention. After completion of the acute Stage 1 procedure and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants in Stage 2 will continue to receive active or sham stimulation according to their initial group allocation;
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 48 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
- Yun-En Liu, MD, Study chair, Shenyang Medical CollegeLin Tao, MM, Principal investigator, Shenyang Medical CollegeFei Meng, MD, Study director, Central Hospital Affiliated to Shenyang Medical Collage
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07233278
- Sponsor's protocol ID
- 2025-038-02_V2
- Status last verified
- Dec 2025
- First submitted
- 14 Nov 2025
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data, study protocol and supporting materials will be made publicly available at the time of formal publication. Data will be hosted on an internationally recognised third-party repository and accessible for non-commercial scientific use.
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-intensity, Low-frequency Periodic rTMS Over the Right Dorsolateral Prefrontal Cortex for Acute Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss and Generalized Anxiety Disorder: a Randomized, Sham-controlled Mechanistic Trial (NEURO-CARD-rTMS-2)
- ClinicalTrials.gov ID
- NCT07233278
- Acronym / sponsor ID
- 2025-038-02_V2
- Conditions
- Recurrent Pregnancy Loss(RPL), Anxiety
- Keywords
- Recurrent pregnancy loss, Anxiety, Dorsolateral Prefrontal Cortex, Cardiac Autonomic Regulation, repetitive transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Shenyang Medical CollegeUniversity, hospital or other
- Study start
- 19 Nov 2025 (actual)
- Primary completion
- 22 Jul 2026 (actual)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 18 Nov 2025 (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 determine whether high-intensity, low-frequency periodic repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) can modulate cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety. The main questions it aims to answer are:
Does 120% resting motor threshold (RMT) rhythmic low-frequency rTMS reduce heart rate during stimulation time windows compared with sham stimulation?
Does 120% RMT rTMS alter heart-rate-variability (HRV) spectral power at the target frequency (0.0167 Hz) compared with sham stimulation?
Researchers will compare active rTMS with sham rTMS to determine whether the active intervention produces measurable changes in cardiac autonomic activity.
Participants will:
Undergo a single session of rTMS or sham stimulation consisting of 20 consecutive stimulation time windows (each 60 seconds: 40 seconds of 1-Hz stimulation plus 20 seconds of rest) targeting the right DLPFC;
Have continuous electrocardiography (ECG) recordings collected during the entire stimulation session;
Complete clinical and psychiatric assessments before participation.
Detailed description
For this protocol, recurrent pregnancy loss (RPL) was defined as two or more consecutive spontaneous miscarriages before 28 weeks of gestation. RPL affects approximately 2-5% of reproductive-age couples worldwide and imposes a substantial clinical and emotional burden. Beyond its implications for reproductive health, RPL is increasingly recognized as a condition associated with systemic consequences, including heightened anxiety, altered autonomic nervous system function, and increased long-term cardiovascular risk.
Emerging evidence suggests that in women with RPL and comorbid anxiety, chronic psychological stress may lead to dysregulation of the autonomic nervous system, characterized by increased sympathetic tone, reduced vagal activity, elevated resting heart rate, and decreased heart rate variability (HRV). These alterations may create a maladaptive feedback loop that reinforces emotional distress, autonomic imbalance, and reproductive vulnerability.
To address this issue, this randomized, sham-controlled, proof-of-concept clinical trial will investigate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right dorsolateral prefrontal cortex (DLPFC)-a region critically involved in emotion regulation and autonomic control-can modulate cardiac autonomic function in women with RPL and anxiety.
The intervention protocol is based on findings from a prior dose-finding study (NEURO-CARD-rTMS-1), which indicated that stimulation at 120% of resting motor threshold (RMT) produced significant reductions in heart rate without compromising tolerability. Building on this, the current trial (NEURO-CARD-rTMS-2) will apply 1-Hz rhythmic rTMS at 120% RMT over the right DLPFC, delivered in 20 consecutive stimulation windows (each 60 seconds long: 40 seconds of stimulation followed by 20 seconds of rest). This stimulation paradigm aligns with the very-low-frequency (VLF) band of HRV (~0.0167 Hz), enabling frequency-specific entrainment analysis.
The primary endpoint will be the difference in baseline-corrected mean heart rate during the stimulation time windows between the active and sham groups. Secondary endpoints include changes in HRV spectral power at 0.0167 Hz and brain-heart coupling (BHC), defined as the correlation between heart rate and spectral power at this frequency. Safety outcomes will be monitored throughout the procedure.
All electrocardiographic (ECG) data will be recorded continuously at 1000 Hz using a wireless Bluetooth system. Participants will undergo standardized psychiatric assessments based on DSM-5 criteria, and key demographic and clinical variables (e.g., BMI, blood pressure, medication use, number and cause of miscarriages) will be collected for covariate analysis.
This trial aims to provide initial mechanistic evidence for the feasibility and physiological efficacy of right DLPFC-targeted neuromodulation in improving autonomic regulation in a high-risk, psychologically sensitive population. If successful, the findings will support the development of non-invasive, brain-based interventions to improve both reproductive and cardiovascular outcomes in women with RPL and anxiety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- This study will use a parallel assignment interventional model. Participants will be randomly assigned in a 1:1 ratio to either the active rTMS group or the sham rTMS group.In Stage 1, each participant will receive a single-session intervention under their assigned condition. The intervention will be delivered in a controlled laboratory setting, and both groups will undergo identical procedures except for the presence or absence of effective magnetic stimulation. This design allows for between-group comparison of physiological responses and safety outcomes attributable to the intervention. After completion of the acute Stage 1 procedure and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants in Stage 2 will continue to receive active or sham stimulation according to their initial group allocation;
| Arm | Type | Receives |
|---|---|---|
| real rTMS group | Active comparator | Device: Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cyclesParticipants in this arm will receive active repetitive transcranial magnetic stimulation (rTMS) delivered to the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the stimulation protocol consists of 20 consecutive cycles of low-frequency (1 Hz) rTMS at 120% of the resting motor threshold (RMT), with each cycle comprising 40 seconds of stimulation followed by 20 seconds of rest. The total stimulation duration is approximately 20 minutes. Real stimulation is applied with the figure-of-eight coil positioned tangentially to the scalp. After completion of Stage 1 and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants who enter Stage 2 will continue to receive active stimulation under the same fixed-parameter framework; no re-randomization will be performed. |
| sham rTMS group | Sham comparator | Device: Sham rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cyclesParticipants in this arm will receive sham repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the stimulation protocol mimics the active condition in timing and coil placement but involves tilting the coil at a 45-degree angle to the scalp, significantly attenuating magnetic field penetration. This approach preserves the auditory and tactile sensations of stimulation without producing cortical effects. The procedure consists of 20 consecutive cycles of sham stimulation, each comprising 40 seconds of simulated stimulation followed by 20 seconds of rest, lasting approximately 20 minutes in total. After completion of Stage 1 and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants who enter Stage 2 will continue to receive sham stimu |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- (i) Female, aged 18-45 years, and right-handed;
- (ii) Diagnosed with recurrent pregnancy loss (RPL), defined as two or more consecutive spontaneous miscarriages occurring before 28 weeks of gestation;
- (iii) Not currently pregnant or in a state of missed miscarriage;
- (iv) Meeting the DSM-5 diagnostic criteria for GAD, with a HAMA score of at least 16, a CGI-S score of at least 4, and a HAMD-17 score of no more than 17.
Key exclusion criteria (5 listed)
- (i) Contraindications to transcranial magnetic stimulation (TMS), such as metallic implants or a history of epilepsy;
- (ii) Unstable blood pressure (systolic >180 mmHg or <90 mmHg);
- (iii) Coexisting major organic disorders, including hyperthyroidism, atrial fibrillation, valvular heart disease, sinus bradycardia, neurological diseases, cerebrovascular disease, or pulmonary disorders;
- (iv) Significant suicide risk;
- (v) Other current major psychiatric disorders, including substance use disorder, schizophrenia, delusional disorder, unspecified psychotic disorder, bipolar disorder, or delirium. To preserve diagnostic homogeneity of the study sample, participants whose current primary diagnosis is another anxiety-related disorder will also be excluded, including panic disorder, social anxiety disorder, separation anxiety disorder, specific phobia, obsessive-compulsive and related disorders, and trauma- and stressor-related disorders; Current use of psychotropic medication at screening, or continuous use within the 4 weeks before screening of antidepressants, anxiolytics, antipsychotics, mood stabilizers, or sedative-hypnotics, in order to minimize hemodynamic confounding.
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 |
|---|---|---|
| Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cyclesParticipants assigned to the active rTMS group will receive rhythmic low-frequency repetitive transcranial magnetic stimulation applied over the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the intervention consists of 20 consecutive stimulation cycles, each comprising 40 seconds of 1 Hz stimulation followed by a 20-second inter-cycle interval, for a total of 60 seconds per cycle. The stimulation intensity is set at 120% of the individual resting motor threshold (RMT). A figure-of-eight coil will be positioned tangentially over the scalp at the targeted right DLPFC site. Electrocardiogram (ECG) signals will be recorded continuously throughout the session. After completion of the acute Stage 1 procedure and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original randomized assignment. Participants who enter Stage 2 will cont | Device | real rTMS group |
| Sham rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cyclesParticipants assigned to the sham rTMS group will receive sham rhythmic low-frequency repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex (DLPFC). In Stage 1, the sham procedure matches the active condition in timing, coil position, and auditory and tactile experience, with 20 consecutive sham stimulation cycles, each comprising 40 seconds of simulated stimulation followed by a 20-second inter-cycle interval, for a total of 60 seconds per cycle. The coil will be held at a 45-degree angle to the scalp to minimize effective cortical stimulation while preserving the sensory characteristics of the procedure. Electrocardiogram (ECG) signals will be recorded continuously throughout the session. After completion of the acute Stage 1 procedure and the post-procedure safety observation period, participants may voluntarily enter a prespecified exploratory Stage 2 subgroup for 4 weeks of continued treatment and follow-up while remaining in their original ran | Device | sham rTMS group |
Primary outcome
The primary endpoint will be the between-group difference in baseline-corrected mean heart rate, averaged across stimulation time windows.
Time frame: Session 1 (Day 1)
Heart rate (HR) will be continuously recorded via ECG (1,000 Hz) during a single rTMS session comprising 20 stimulation cycles (each 60 s: 40 s stimulation at 1 Hz, then 20 s rest). For each cycle, a 50-s analysis window will be defined (-10 s to 0 s pre-stimulation baseline; 0 s to +40 s post-stimulation). Baseline-corrected mean HR for each cycle will be computed as the mean HR in the post-stimulation segment (0-40 s) minus the mean HR in the 10-s pre-stimulation baseline (-10-0 s). Per-participant values will then be averaged across the 20 stimulation time windows, and the primary endpoint will compare these averaged baseline-corrected means between the active and sham rTMS groups.
5 secondary outcomes
The between-group difference in heart rate variability (HRV) spectral power at the target frequency (0.0167 Hz), averaged across stimulation time windows.
Time frame: Session 1 (Day 1)
The strength of the linear correlation between baseline-corrected mean heart rate and spectral power at 0.0167 Hz, averaged across stimulation time windows, in the active rTMS group.
Time frame: Session 1 (Day 1)
The strength of the linear correlation between baseline-corrected mean heart rate and spectral power at 0.0167 Hz, averaged across stimulation time windows, in the sham rTMS group.
Time frame: Session 1 (Day 1)
Incidence of mild adverse events during rTMS stimulation, including scalp discomfort at the stimulation site, facial muscle twitching, mild headache, and dizziness.
Time frame: Session 1 (Day 1)
Incidence of serious adverse events during rTMS stimulation, including syncope and seizures.
Time frame: Session 1 (Day 1)
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 28 Aug 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data, study protocol and supporting materials will be made publicly available at the time of formal publication. Data will be hosted on an internationally recognised third-party repository and accessible for non-commercial scientific use.
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Noninvasive Implantation Potential vs Morphology-Based Selection in IVF Single Blastocyst Transfer
Advanced Age, Recurrent Pregnancy Loss(RPL)
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.
Yun-En Liu, MD study chair
Shenyang Medical College
Lin Tao, MM principal investigator
Shenyang Medical College
Fei Meng, MD study director
Central Hospital Affiliated to Shenyang Medical Collage
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles in people with Recurrent Pregnancy Loss(RPL) and Anxiety, run by Shenyang Medical College at 3 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 4 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 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 primary endpoint will be the between-group difference in baseline-corrected mean heart rate, averaged across stimulation time windows. (time frame: Session 1 (Day 1)). 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 28 Aug 2026.