RecruitingNot ApplicableNCT07233278

High-Intensity, Low-Frequency Periodic rTMS Over the Right Dorsolateral Prefrontal Cortex on Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss and Anxiety

Effects of 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 Randomized, Sham-Controlled, Proof-of-Concept Trial (NEURO-CARD-rTMS-2)

Sponsor

Shenyang Medical College

Enrollment

46 participants

Start Date

Nov 17, 2025

Study Type

INTERVENTIONAL

Conditions

Anxiety Recurrent Pregnancy Loss(RPL)

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. 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.

Eligibility

Sex: FEMALEMin Age: 18 YearsMax Age: 45 Years

Inclusion Criteria4

(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 diagnostic criteria for an anxiety disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

Exclusion Criteria5

(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 psychiatric disorders, including substance use disorders, schizophrenia, delusional disorder, unspecified psychotic disorder, bipolar disorder, or delirium.

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Interventions

DEVICERhythmic repetitive transcranial magnetic stimulation (rTMS) at 120% RMT, 1 Hz, 60-s cycles

Participants in the real rTMS group will receive rhythmic low-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the right dorsolateral prefrontal cortex (DLPFC). The intervention consists of 20 consecutive stimulation cycles, each comprising 40 seconds of 1 Hz stimulation followed by a 20-second inter-cycle interval, totaling 60 seconds per cycle. The stimulation intensity is set at 120% of the individual's 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 synchronously throughout the session for heart rate variability analysis.