Clinical trial

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

Opening soon · Not applicable · 1 countries · Registry ID NCT07561931

Opening soonNot applicableInterventional

What this study is about

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.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age18 Years to 45 Years
SexFemale
Healthy volunteersNot accepted
ConditionRecurrent Pregnancy Loss, Overweight , Obesity, Heart-Brain Coupling

Full registry criteria

Inclusion Criteria: * 1.Female participants aged 18-45 years and right-handed. * 2.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. * 3.BMI ≥24 kg/m², classified as overweight or obesity according to the Chinese adult criteria for overweight and obesity. * 4.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. * 5.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. Exclusion Criteria: * 1.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. * 2.Current pregnancy. * 3.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. * 4.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. * 5.Presence of significant suicide risk. * 6.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. * 7.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. * 8.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. * 9.Any other condition judged by the research team to make participation inappropriate.

Treatments and study arms

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.

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.

Primary outcomes

the between-group difference in mean HBC across 30 stimulation cycles.Day 1

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.

Study locations

1 locations were listed when this page was built. The first 40 are shown.

Central Hospital Affiliated to Shenyang Medical College🇨🇳 Shenyang, Liaoning, China
Fei Meng, MDContact