High-intensity, low-frequency rTMS to the right prefrontal cortex for heart-rate control 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)

This test will see if a single session of high-intensity, low-frequency rTMS to the right dorsolateral prefrontal cortex can change heart rate and heart-rate variability in women with recurrent pregnancy loss who have anxiety.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Shenyang Medical College (other)
• Locations: 2 sites (Shenyang, Liaoning and 1 other locations)
• Trial ID: NCT07233278 on ClinicalTrials.gov

What this trial studies

This is a randomized, sham-controlled, proof-of-concept trial that delivers a single session of rhythmic low-frequency rTMS (120% resting motor threshold, 1 Hz) to the right dorsolateral prefrontal cortex with 20 consecutive 60-second stimulation windows. Participants are women aged 18–45 with a history of two or more pregnancy losses and a DSM-5 anxiety disorder, and they are compared to a matched sham stimulation group. The primary physiological outcomes are within-session heart rate changes and heart-rate-variability spectral power at the target rhythm (0.0167 Hz). The protocol builds on a prior dose-finding study and focuses on short-term modulation of cardiac autonomic markers rather than reproductive outcomes.

Who should consider this trial

Good fit: Women aged 18–45, right-handed, not currently pregnant, with at least two prior pregnancy losses before viability and a DSM-5 anxiety disorder, who have no contraindications to TMS, would be ideal candidates.

Not a fit: People who are male, currently pregnant, have major organic cardiac or neurologic conditions, active substance use or other excluded psychiatric disorders, or contraindications to TMS are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the intervention could offer a noninvasive way to lower sympathetic drive and improve heart-rate variability in women with recurrent pregnancy loss and anxiety, potentially reducing stress-related cardiovascular risk.

How similar studies have performed: Early dose-finding work and small rTMS studies have shown that prefrontal stimulation can alter autonomic metrics, but this specific high-intensity, low-frequency rhythmic protocol for RPL with anxiety is a novel, proof-of-concept application.

Eligibility criteria

Inclusion Criteria:

* (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 Criteria:

* (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.

Where this trial is running

Shenyang, Liaoning and 1 other locations

• The Second Affiliated Hospital of Shenyang Medical College — Shenyang, Liaoning, China (RECRUITING)
• Central Hospital Affiliated to Shenyang Medical College — Shenyang, Liaoning, China (RECRUITING)

Study contacts

• Principal investigator: Lin Tao, MM — Shenyang Medical College
• Study coordinator: Fei Meng, MD

Conditions: Recurrent Pregnancy Loss, Anxiety, Recurrent pregnancy loss, Dorsolateral Prefrontal Cortex, Cardiac Autonomic Regulation, repetitive transcranial magnetic stimulation