Right Prefrontal Autonomic Mapping in Recurrent Pregnancy Loss With Comorbid Anxiety
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorShenyang Jinghua Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 and Hamilton Depression Rating Scale (HAMD-17) score ≤17 (to exclude clinically significant depression).
Disqualifiers
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)Current use of psychotropic medications at the time of screening, to avoid hemodynamic or autonomic confounding;
Trial design
Design model
Single group
Treatments tested in this trial
repetitive transcranial magnetic stimulation(rTMS)
DeviceParticipants 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.
Treatment groups
55 Participants
are divided into 1 treatment groupGroup A: Right DLPFC rTMS-ECG intensity-sweep protocolExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
Day 1Secondary outcomes
1
Mean normalized wavelet power near the frequency of the 60-s stimulation cycle (0.016-0.017 Hz)
The primary spectral analysis will use the Morlet wavelet to extract mean normalized wavelet power near the frequency of the 60-s stimulation cycle (0.016-0.017 Hz) from the ECG-derived R-R interval time series and to compare this measure across the six stimulation intensity conditions. This outcome will be used to assess whether ECG dynamics show a response near the frequency of the 60-s stimulation cycle and will not be used as evidence of strict physiological entrainment.
Time frame
Day 12
rTMS-induced cardiac coupling index at each stimulation intensity
At each stimulation intensity, the rTMS-induced cardiac coupling index will be defined as the Pearson correlation coefficient across participants between decreased HR and mean normalized wavelet power near the frequency of the 60-s stimulation cycle (0.016-0.017 Hz). This index will quantify the consistency between directional heart-rate change and power aggregation near the frequency of the 60-s stimulation cycle across stimulation intensities. Because heart-rate reduction will be represented by more negative decreased HR values and power aggregation near the frequency of the 60-s stimulation cycle will be represented by higher normalized power values, an intensity condition in which participants with greater heart-rate reduction also show higher power near the frequency of the 60-s stimulation cycle will produce a negative correlation pattern. This index will be used as a parameter-level quantitative measure and will not be interpreted as direct evidence of strict physiological entr
Time frame
Day 13
Incidence of non-serious adverse events
The study will record pain at the stimulation site, transient facial muscle contractions, headache, dizziness, presyncope, other participant-reported discomfort, and other investigator-observed non-serious adverse events.
Time frame
Day 14
Incidence of serious adverse events
The study will record serious adverse events occurring during the procedure or during the post-procedure observation period, including syncope, seizure, and any other event requiring medical intervention or leading to termination of the study procedure.
Time frame
Day 1Sponsors and contacts
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Shenyang Jinghua Hospital
Lead sponsor
Shenyang Medical College
Sponsor institution
Source ClinicalTrials.gov