High-intensity low-frequency rTMS over the right prefrontal cortex to target anxiety and heart regulation in women with recurrent pregnancy loss

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 Proof-of-Concept rTMS-ECG Clinical Trial (NEURO-CARD-rTMS-1)

This trial will try high-intensity, low-frequency rTMS to the right dorsolateral prefrontal cortex to see if it improves heart rate regulation and reduces anxiety in women with recurrent pregnancy loss.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Shenyang Jinghua Hospital (Industry-sponsored)
• Locations: 3 sites (Shenyang, Liaoning and 2 other locations)
• Trial ID: NCT06968026 on ClinicalTrials.gov

What this trial studies

This proof-of-concept interventional trial applies high-intensity, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex in women with recurrent pregnancy loss (RPL) and clinically significant anxiety. Participants undergo a sequential stimulation paradigm while real-time ECG is recorded to measure acute changes in heart rate and heart rate variability as markers of autonomic modulation. The protocol identifies the stimulation intensity that produces the strongest autonomic effect and compares cardiac responses across sessions. Results will inform whether right-DLPFC-targeted rTMS can transiently reduce sympathetic tone and guide future trials of neuromodulation for anxiety and autonomic dysfunction in RPL.

Who should consider this trial

Good fit: Women aged 18–45 who are right-handed, have a history of two or more consecutive spontaneous miscarriages, are currently non-pregnant or have a missed abortion, meet criteria for a DSM-5 anxiety disorder with HAMA ≥14 and HAMD-17 ≤17, and can attend in-person rTMS sessions are the intended participants.

Not a fit: People with major depressive disorder beyond the HAMD cutoff, contraindications to TMS (for example metallic implants or epilepsy), men, those outside the age range, or those whose autonomic dysfunction stems from non-anxiety medical causes are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could offer a noninvasive neuromodulation option to reduce anxiety and normalize cardiac autonomic function, potentially improving emotional well-being and reproductive outcomes for affected women.

How similar studies have performed: Previous rTMS research has shown mood and autonomic effects in other disorders, but using high-intensity, low-frequency right-DLPFC rTMS specifically for anxiety and cardiac autonomic dysfunction in RPL is a novel, largely untested approach.

Eligibility criteria

Inclusion Criteria:

1. Female, aged 18-45 years, and right-handed.
2. Diagnosis of recurrent pregnancy loss (RPL), defined as ≥2 consecutive spontaneous miscarriages before 28 weeks of gestation.
3. Currently non-pregnant, or presenting with a missed abortion (no fetal cardiac activity confirmed by ultrasound).
4. Hamilton Anxiety Rating Scale (HAMA) score ≥14 (moderate or greater anxiety) and Hamilton Depression Rating Scale (HAMD-17) score ≤17 (to exclude clinically significant depression).
5. Confirmed diagnosis of at least one DSM-5 anxiety disorder subtype-generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), or post-traumatic stress disorder (PTSD)-based on a structured or semi-structured psychiatric interview conducted remotely via HIPAA-compliant, encrypted video by a board-certified psychiatrist.--Exclusion Criteria:

1\) Contraindications to transcranial magnetic stimulation (TMS), including metallic implants or a history of epilepsy; 2) Uncontrolled blood pressure (systolic \>180 mmHg or \<90 mmHg); 3) Presence of other major medical conditions, including hyperthyroidism, a history of atrial fibrillation, valvular heart disease, sinus bradycardia, neurological disorders, cerebrovascular disease, or chronic pulmonary disease; 4) Clinically significant suicide risk; 5) A current or past diagnosis of 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 2 other locations

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

Study contacts

• Principal investigator: Lin Tao, MM — Shenyang Medical College
• Study coordinator: Yun-En Liu, MD

Conditions Recurrent Pregnancy Loss; Anxiety Disorders; Recurrent pregnancy loss; anxiety disorders; repetitive transcranial magnetic stimulation; dorsolateral prefrontal cortex; autonomic modulation