Right Prefrontal Autonomic Mapping in Recurrent Pregnancy Loss With Comorbid Anxiety

NCT06968026 | Completed DMC

• 1 other identifier: 2025-0522_V2
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 4

Brief Summary

Recurrent pregnancy loss is often accompanied by substantial anxiety and may also be associated with autonomic imbalance and increased long-term cardiovascular vulnerability. The present proof-of-concept rTMS-ECG parameter-finding trial will examine whether high-intensity, low-frequency, periodic repetitive transcranial magnetic stimulation (rTMS) delivered over the right dorsolateral prefrontal cortex can induce detectable acute cardiac autonomic responses in women with recurrent pregnancy loss and comorbid anxiety disorders. A total of 55 women will be enrolled. During a single experimental session, each participant will undergo a stimulation-intensity sweep protocol with six consecutive stimulation cycles at 100%, 110%, 120%, 130%, 140%, and 150% of resting motor threshold. Each cycle will consist of 40 seconds of 1 Hz stimulation followed by a 20-second rest interval, while electrocardiography will be recorded continuously throughout the procedure. The study will evaluate baseline-corrected heart-rate change, wavelet-derived power near the stimulation-cycle frequency, and the rTMS-induced cardiac coupling index across intensity conditions. The goal is to identify the candidate stimulation intensity that produces the most detectable and physiologically consistent acute cardiac autonomic response for transfer to subsequent NEURO-CARD-rTMS studies.

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 (1)

• Baseline-corrected heart-rate change across stimulation intensity conditions

  decreased HR will be calculated separately for each stimulation intensity condition to assess the acute cardiac autonomic response induced by escalating low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC). Within each stimulation cycle, the mean heart rate during the 10 s immediately before stimulation onset will be used as the baseline, and the mean heart-rate change during the subsequent 40 s stimulation period will be calculated relative to this baseline. More negative values will indicate greater heart-rate reduction induced by the corresponding stimulation intensity. The primary analysis will compare decreased HR across the six intensity conditions, 100%, 110%, 120%, 130%, 140%, and 150% resting motor threshold (RMT), with 100% RMT serving as the within-subject threshold-reference condition.

  Day 1

Secondary Outcomes (4)

• Mean normalized wavelet power near the frequency of the 60-s stimulation cycle (0.016-0.017 Hz)

  Day 1

• rTMS-induced cardiac coupling index at each stimulation intensity

  Day 1

• Incidence of non-serious adverse events

  Day 1

• Incidence of serious adverse events

  Day 1

Study Arms (1)

Right DLPFC rTMS-ECG intensity-sweep protocol

EXPERIMENTAL

Single-group, within-subject, repeated-measures proof-of-concept trial. Eligible participants will undergo one right dorsolateral prefrontal cortex (DLPFC) rTMS-ECG intensity-sweep session consisting of six consecutive stimulation cycles delivered sequentially from 100% to 150% of resting motor threshold (RMT) in 10% increments. Each cycle will include 40 s of 1 Hz stimulation followed by a 20 s intertrain interval. Continuous ECG will be recorded throughout the procedure.

Device: repetitive transcranial magnetic stimulation(rTMS)

Interventions

repetitive transcranial magnetic stimulation(rTMS) DEVICE

Participants will undergo a right DLPFC rTMS intensity-sweep protocol with simultaneous electrocardiography (ECG) recording. After a 20 s prestimulation resting baseline, six consecutive stimulation cycles will be delivered at 100%, 110%, 120%, 130%, 140%, and 150% of individual resting motor threshold (RMT). Each cycle will consist of 40 s of 1 Hz stimulation followed by a 20 s intertrain interval, forming a 60 s stimulation-locked cycle. The maximum stimulation intensity will not exceed 85% of maximum stimulator output.

Right DLPFC rTMS-ECG intensity-sweep protocol

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• 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 and Hamilton Depression Rating Scale (HAMD-17) score ≤17 (to exclude clinically significant depression).
• )Diagnosis of generalized anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis will be established through a structured diagnostic interview conducted by a qualified attending-level or senior psychiatrist, either on site or, when on-site assessment cannot be completed, through a secure encrypted video-conferencing platform with multidisciplinary team support.

You may not qualify if:

• \) Contraindications to transcranial magnetic stimulation (TMS), including metallic implants or a history of epilepsy;
• \) Uncontrolled blood pressure (systolic \>180 mmHg or \<90 mmHg);
• \) 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;
• )Current use of psychotropic medications at the time of screening, to avoid hemodynamic or autonomic confounding;
• \) Clinically significant suicide risk;
• \) 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

Study Sites (4)

242 Hospital Affiliated to Shenyang Medical College

Shenyang, Liaoning, 110000, China

Location

The Second Affiliated Hospital of Shenyang Medical College

Shenyang, Liaoning, 110001, China

Location

Shenyang Jinghua Hospital

Shenyang, Liaoning, China, China

Location

Central Hospital Affiliated to Shenyang Medical College

Shenyang, Liaoning, China

Location

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

Study Design

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

Model Details: Single-group, within-subject, repeated-measures parameter-finding study. All participants will undergo the same right DLPFC rTMS-ECG intensity-sweep protocol, consisting of six consecutive stimulation cycles delivered sequentially from 100% to 150% of resting motor threshold in 10% increments. Each cycle will include 40 s of 1 Hz stimulation followed by a 20 s intertrain interval.

Study Record Dates

• First Submitted: May 3, 2025
• First Posted: May 13, 2025
• Study Start: May 16, 2025
• Primary Completion: October 20, 2025
• Study Completion: October 20, 2025
• Last Updated: July 7, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Available at the time of publication of the final article

Locations

CN (4)