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)

NCT ID: NCT06968026

Last Updated: 2025-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-16

Study Completion Date

2026-03-30

Brief Summary

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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.

Detailed Description

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Recurrent pregnancy loss (RPL) is frequently associated with persistent anxiety and cardiac autonomic dysregulation, forming a vicious cycle that impacts emotional and reproductive outcomes. Neuroimaging studies suggest that lateralised dysfunction of the dorsolateral prefrontal cortex (DLPFC) contributes to both emotional dysregulation and sympathetic overactivation.

Building upon the proposed Brain-Heart-Emotion interaction model, we hypothesise that excessive right DLPFC activity amplifies emotional arousal and cardiac sympathetic drive, while insufficient left DLPFC regulation fails to provide cognitive control over anxiety. This imbalance may underlie the comorbidity of anxiety and autonomic dysfunction in women with RPL.

This proof-of-concept clinical trial applies high-intensity, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right DLPFC, aiming to assess its acute neurocardiac effects, specifically rTMS-induced changes in heart rate and heart rate variability (HRV)-two key indicators of autonomic modulation.

By using a sequential stimulation paradigm combined with real-time ECG acquisition, this trial will identify the optimal intensity threshold for autonomic modulation and determine whether right DLPFC-targeted rTMS can transiently reduce cardiac sympathetic tone.

Findings from this study will inform future trials evaluating rTMS as a precision treatment for anxiety and autonomic dysfunction in RPL, potentially improving psychophysiological health and pregnancy outcomes without relying on pharmacotherapy.

Conditions

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Recurrent Pregnancy Loss Anxiety Disorders

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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rTMS Intervention

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

Group Type EXPERIMENTAL

repetitive transcranial magnetic stimulation(rTMS)

Intervention Type 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.

Interventions

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repetitive transcranial magnetic stimulation(rTMS)

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.

Intervention Type DEVICE

Eligibility Criteria

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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).

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Central Hospital Affiliated to Shenyang Medical Collage

OTHER

Sponsor Role collaborator

Shenyang Medical College

OTHER

Sponsor Role collaborator

The Second Hospital of Shenyang Medical College

OTHER

Sponsor Role collaborator

242 Hospital Affiliated to Shenyang Medical College

UNKNOWN

Sponsor Role collaborator

Shenyang Jinghua Hospital

INDUSTRY

Sponsor Role lead

Responsible Party

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Lin Tao

Assoc. Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lin Tao, MM

Role: PRINCIPAL_INVESTIGATOR

Shenyang Medical College

Yun-En Liu, MD

Role: STUDY_CHAIR

Shenyang Medical College

Locations

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The Second Affiliated Hospital of Shenyang Medical College

Shenyang, Liaoning, China

Site Status RECRUITING

Shenyang Jinghua Hospital

Shenyang, Liaoning, China

Site Status RECRUITING

Central Hospital Affiliated to Shenyang Medical Collage

Shenyang, Liaoning, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yun-En Liu, MD

Role: CONTACT

86-24-62215130

Lin Tao, MM

Role: CONTACT

86-18802401698

Facility Contacts

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Xiu-Ling Zhang, MD

Role: primary

86-24-31236568 ext. 18002453190

Jing Ge, MD

Role: primary

86-024-66182355 ext. 86-13309883202

Lin Tao, MM

Role: backup

86-18802401698

Fei Meng, MD

Role: primary

86-024-85715635 ext. 86-18002478563

Other Identifiers

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2025-0413

Identifier Type: -

Identifier Source: org_study_id

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