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

NCT06968026 | Recruiting DMC

• 1 other identifier: 2025-0413
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 3

Brief Summary

This proof-of-concept trial investigates whether high-intensity, low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right dorsolateral prefrontal cortex (DLPFC) can improve autonomic cardiac regulation in women with recurrent pregnancy loss (RPL) and anxiety. The study explores the lateralised function of the DLPFC in emotional and autonomic control and tests a novel neuromodulation-based strategy to relieve anxiety and sympathetic overactivation.

Conditions

Recurrent Pregnancy Loss; Anxiety Disorders

Keywords

Recurrent pregnancy loss; anxiety disorders; repetitive transcranial magnetic stimulation; dorsolateral prefrontal cortex; autonomic modulation

Outcome Measures

Primary Outcomes (2)

• Change in baseline-corrected heart rate across stimulation intensities

  Mean baseline-corrected heart rate will be calculated for each stimulation intensity to assess autonomic cardiac responses to increasing low-frequency rTMS intensity

  During six consecutive stimulation trains (each 60 seconds; intensities increasing from 100% to 150% RMT)

• Change in heart rate variability (HRV) spectral power at 0.0167 Hz during rTMS

  HRV spectral power at the entrainment frequency (0.0167 Hz) will be extracted from ECG data and compared across stimulation intensities to assess rhythmic autonomic modulation

  During six consecutive stimulation trains (each 60 seconds; intensities increasing from 100% to 150% RMT

Secondary Outcomes (3)

• Brain-Heart Coupling (BHC) strength at each stimulation intensity

  During six consecutive stimulation trains (100% to 150% RMT)

• Incidence of non-serious adverse events

  Immediately after the rTMS session

• Incidence of serious adverse events

  Immediately after the rTMS session

Study Arms (1)

rTMS Intervention

EXPERIMENTAL

This study is designed as a proof-of-concept clinical trial, employing a within-subject, single-factor repeated-measures design

Device: repetitive transcranial magnetic stimulation(rTMS)

Interventions

repetitive transcranial magnetic stimulation(rTMS) DEVICE

The eligible participants will undergo an intensity sweep consisting of six stimulation trains over the right dorsolateral prefrontal cortex (DLPFC), with stimulation intensities ranging from 100% to 150% of the individual resting motor threshold (RMT), increasing in 10% increments. Each train will last 60 seconds, comprising 40 seconds of active rTMS at 1 Hz and a 20-second intertrain interval (ITI). Synchronous electrocardiogram (ECG) data will be continuously recorded throughout the entire procedure.

rTMS Intervention

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Women with recurrent pregnancy loss and anxiety
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female, aged 18-45 years, and right-handed.
• Diagnosis of recurrent pregnancy loss (RPL), defined as ≥2 consecutive spontaneous miscarriages before 28 weeks of gestation.
• Currently non-pregnant, or presenting with a missed abortion (no fetal cardiac activity confirmed by ultrasound).
• 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).

You may not qualify if:

• \) 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.

Sponsors & Collaborators

• Shenyang Jinghua Hospital: lead
• Central Hospital Affiliated to Shenyang Medical Collage: collaborator
• Shenyang Medical College: collaborator
• The Second Hospital of Shenyang Medical College: collaborator

Study Sites (3)

The Second Affiliated Hospital of Shenyang Medical College

Shenyang, Liaoning, 110001, China

RECRUITING

Shenyang Jinghua Hospital

Shenyang, Liaoning, China, China

RECRUITING

Central Hospital Affiliated to Shenyang Medical Collage

Shenyang, Liaoning, China

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Lin Tao, MM

  Shenyang Medical College

  PRINCIPAL INVESTIGATOR

• Yun-En Liu, MD

  Shenyang Medical College

  STUDY CHAIR

Central Study Contacts

Yun-En Liu, MD

CONTACT

86-24-62215130; lye9901@163.com

Lin Tao, MM

CONTACT

86-18802401698; 1939908868@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof.

Model Details: This study adopts a sequential interventional model in which all participants receive a single-arm intervention consisting of six consecutive stimulation blocks of low-frequency rTMS targeting the right dorsolateral prefrontal cortex (DLPFC). Each participant undergoes stimulation at increasing intensities (100% to 150% of resting motor threshold \[RMT\]) in a fixed, predefined sequence. The design allows for within-subject comparisons across stimulation intensities, with no randomization or crossover between different intervention arms.

Study Record Dates

• First Submitted: May 3, 2025
• First Posted: May 13, 2025
• Study Start: May 16, 2025
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: April 21, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Available at the time of publication of the final article
• Access Criteria: Data will be deposited on the ResMan platform and will be accessible for non-commercial research purposes.

Locations

CN (3)