Effects of High-frequency Left Dorsolateral Prefrontal rTMS on Heart-brain Coupling in Women With Recurrent Pregnancy Loss and Elevated BMI

NCT07561931 | Not Yet Recruiting DMC

• 1 other identifier: 2026-024-02
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, sham-controlled mechanistic trial will examine whether a single session of high-frequency repetitive transcranial magnetic stimulation, rTMS, applied to the left dorsolateral prefrontal cortex can modify heart-brain coupling in women with recurrent pregnancy loss and elevated body mass index, BMI. Women with recurrent pregnancy loss often experience reproductive, metabolic, and emotional stress at the same time, and this combined vulnerability may be associated with altered autonomic regulation and exaggerated cardiac responses to stress. The left dorsolateral prefrontal cortex is a key brain region involved in cognitive control, emotion regulation, and top-down modulation of autonomic function. Eligible participants will be randomly assigned in a 1:1 ratio to receive either real or sham rTMS at the same left dorsolateral prefrontal target. The stimulation protocol will use 10 Hz rTMS at 100% motor threshold, delivered in 30 cycles of 5 s stimulation followed by 11 s inter-train interval, with simultaneous 3-lead electrocardiography recording. The primary endpoint will be the between-group difference in mean heart-brain coupling across 30 stimulation cycles. Safety and tolerability will also be monitored. This study is intended to provide mechanistic evidence and methodological support for future multi-session randomized trials in this population.

Conditions

Recurrent Pregnancy Loss; Overweight , Obesity; Heart-Brain Coupling

Keywords

recurrent pregnancy loss; elevated BMI; overweight; heart-brain coupling; repetitive transcranial magnetic stimulation; left dorsolateral prefrontal cortex; autonomic regulation

Outcome Measures

Primary Outcomes (1)

• the between-group difference in mean HBC across 30 stimulation cycles.

  Heart-brain coupling, HBC, is defined as the power of RR-interval or heart-rate oscillations induced by repeated TMS and locked to the stimulation-cycle frequency at the target frequency, and is used to quantify rhythmic entrainment effects. In this study, HBC is specifically defined as the time-averaged normalized power within the 0.062-0.063 Hz band during each 16 s stimulation cycle. The primary endpoint will be calculated using the Morlet wavelet, with the wavenumber set to the default value of 6 in order to achieve a relative balance between temporal resolution and frequency resolution. For each participant, 30 cycle-specific HBC values will first be obtained, and these 30 values will then be averaged to derive the participant-level mean HBC; this mean will be entered into the between-group comparison as the primary endpoint.

  Day 1

Secondary Outcomes (4)

• Mean HBC across 30 stimulation cycles under the higher-frequency-resolution condition.

  Day 1

• Mean HBC across 30 stimulation cycles under the higher-temporal-resolution condition.

  Day 1

• Repeated analysis using the DoG wavelet.

  Day 1

• Repeated analysis using the Paul wavelet.

  Day 1

Other Outcomes (2)

• General adverse events during rTMS

  Day 1

• Serious adverse events during rTMS

  Day 1

Study Arms (2)

Real rTMS

EXPERIMENTAL

Participants assigned to this arm will receive a single session of real high-frequency rTMS targeting the left dorsolateral prefrontal cortex. Stimulation will be delivered at 10 Hz and 100% motor threshold, with 30 stimulation cycles. Each cycle will include a 5 s train followed by an 11 s inter-train interval. Continuous 3-lead ECG will be recorded during the rTMS-ECG protocol.

Device: Real repetitive transcranial magnetic stimulation

Sham rTMS

SHAM COMPARATOR

Participants assigned to this arm will receive a single session of sham rTMS at the same left dorsolateral prefrontal cortex target. The coil will be angled approximately 45° relative to the scalp to markedly reduce effective cortical stimulation while preserving, as far as possible, the acoustic cue and part of the scalp sensation. Continuous 3-lead ECG will be recorded during the rTMS-ECG protocol.

Device: Sham repetitive transcranial magnetic stimulation

Interventions

Real repetitive transcranial magnetic stimulation DEVICE

Real rTMS will be delivered to the left dorsolateral prefrontal cortex using the adjusted BeamF3 target. The protocol will consist of 10 Hz stimulation at 100% motor threshold, delivered in 30 cycles, with each cycle including a 5 s train and an 11 s inter-train interval. The total number of pulses will be 1,500. Continuous 3-lead ECG will be recorded during stimulation.

Also known as: real rTMS

Real rTMS

Sham repetitive transcranial magnetic stimulation DEVICE

Sham rTMS will be delivered at the same left dorsolateral prefrontal cortex target as the real-rTMS condition. The coil will be positioned at approximately 45° relative to the scalp to reduce effective cortical stimulation while preserving, as far as possible, the acoustic cue and part of the scalp sensation. Continuous 3-lead ECG will be recorded during the sham protocol.

Also known as: sham rTMS

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female participants aged 18-45 years and right-handed.
• Fulfillment of the prespecified definition of recurrent pregnancy loss in this study, defined as at least two consecutive spontaneous miscarriages occurring before 28 weeks of gestation.
• BMI ≥24 kg/m², classified as overweight or obesity according to the Chinese adult criteria for overweight and obesity.
• Currently not pregnant and in a clinically stable condition. If there is a recent history of missed abortion, appropriate management must have been completed and obstetric assessment must confirm the absence of acute vaginal bleeding, infection, marked abdominal pain, or hemodynamic instability.
• Ability to understand the study procedures, provide written informed consent, and cooperate with scale assessment, transcranial magnetic stimulation safety screening, and the single-session rTMS-ECG protocol.

You may not qualify if:

• Presence of contraindications to transcranial magnetic stimulation or elevated seizure risk, including but not limited to epilepsy or a history of unexplained seizures, intracranial ferromagnetic metal implantation, or the presence of electronic or metallic implanted devices within 30 cm of the coil that are judged unsuitable for transcranial magnetic stimulation.
• Current pregnancy.
• Hemodynamic instability or cardiovascular abnormalities that may substantially affect interpretation of the primary endpoint, including systolic blood pressure \>180 mmHg or \<90 mmHg, atrial fibrillation or other clinically significant arrhythmias, valvular heart disease, marked sinus bradycardia, symptomatic coronary artery disease, or other cardiovascular conditions judged by the research team to make participation unsuitable.
• Uncontrolled major medical or neurologic disorders, particularly those that may substantially affect autonomic state, ECG recording, or interpretation of the primary endpoint, including uncontrolled thyroid dysfunction, uncontrolled diabetes mellitus, significant cerebrovascular disease, neurologic disorders, or active pulmonary disease.
• Presence of significant suicide risk.
• Severe psychiatric disorders that may affect study safety or adherence, including schizophrenia spectrum disorders, bipolar disorder during a manic or hypomanic episode, delirium, and active substance use disorder.
• Severe anxiety or severe depression, defined as a Hamilton Anxiety Rating Scale total score of ≥25 or a 17-item Hamilton Depression Rating Scale total score of ≥24.
• Recent medication-related confounding risk, including current withdrawal from alcohol, sedative-hypnotics, or other relevant substances, or initiation, discontinuation, or dose adjustment within the preceding 2 weeks of medications that may substantially affect seizure threshold, autonomic function, ECG-related indices, or interpretation of the primary endpoint.
• Any other condition judged by the research team to make participation inappropriate.

Sponsors & Collaborators

• Shenyang Medical College: lead

Study Sites (1)

Central Hospital Affiliated to Shenyang Medical College

Shenyang, Liaoning, 110024, China

Location

MeSH Terms

Conditions

Overweight; Obesity

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Yun-En Liu, MD

  Shenyang Medical College

  STUDY CHAIR

• Lin Tao, MM

  Shenyang Medical College

  PRINCIPAL INVESTIGATOR

• Fei Meng, MD

  Central Hospital Affiliated to Shenyang Medical Collage

  STUDY DIRECTOR

Central Study Contacts

Lin Tao, MM

CONTACT

86-18802401698; 1939908868@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants, data collectors, outcome assessors, and statistical analysts will be masked to group assignment. The operator delivering rTMS will not be masked because the real and sham coil positions require different handling. Group allocation will not be disclosed to participants or masked study personnel during data collection and analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.

Model Details: Participants will be randomly assigned in a 1:1 ratio to one of two parallel groups: real rTMS or sham rTMS. Both groups will undergo a single-session rTMS-ECG protocol targeting the left dorsolateral prefrontal cortex. The real-rTMS group will receive high-frequency 10 Hz stimulation at 100% motor threshold. The sham-rTMS group will receive stimulation at the same scalp target with the coil angled approximately 45° relative to the scalp to reduce effective cortical stimulation while preserving acoustic and partial scalp sensory cues.

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: May 1, 2026
• Study Start: April 28, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE

Locations

CN (1)