Clinical trials

The goal of this clinical trial is to determine whether high-intensity, low-frequency periodic repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex (DLPFC) can modulate cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety. The main questions it aims to answer are: Does 120% resting motor threshold (RMT) rhythmic low-frequency rTMS reduce heart rate during stimulation time windows compared with sham stimulation? Does 120% RMT rTMS alter heart-rate-variability (HRV) spectral power at the target frequency (0.0167 Hz) compared with sham stimulation? Researchers will compare active rTMS with sham rTMS to determine whether the active intervention produces measurable changes in cardiac autonomic activity. Participants will: Undergo a single session of rTMS or sham stimulation consisting of 20 consecutive stimulation time windows (each 60 seconds: 40 seconds of 1-Hz stimulation plus 20 seconds of rest) targeting the right DLPFC; Have continuous electrocardiography (ECG) recordings collected during the entire stimulation session; Complete clinical and psychiatric assessments before participation.

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.

The goal of this clinical trial is to learn whether right dorsolateral prefrontal cortex (right DLPFC)-targeted fNIRS-BCI online closed-loop neurofeedback, delivered with slow-wave acoustic cueing, can reduce anxiety symptoms and improve cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety (women aged 18-45 years, right-handed, currently not pregnant or in a missed miscarriage state). The main questions it aims to answer are: Does real neurofeedback increase the proportion of participants who achieve an anxiety treatment response (defined as ≥50% reduction in Hamilton Anxiety Rating Scale \[HAMA\] total score from baseline) compared with sham feedback, at end of treatment and at 3-month follow-up? Is the intervention safe and well tolerated, as reflected by between-group differences in adverse events during the training period? Do brain and autonomic measures show between-group differences during the first formal session, including right DLPFC HbO downregulation, interhemispheric DLPFC synchronisation, heart rate (HR), and heart rate variability (HRV) indices? Researchers will compare real right DLPFC neurofeedback to sham feedback (identical procedures and displays but weakened coupling to real-time neural activity) to see if real neurofeedback improves anxiety outcomes and brain-heart autonomic regulation. Participants will: Complete screening, baseline clinical assessments, and physical examination Be randomly assigned (1:1) to real neurofeedback or sham feedback Complete 3 days of adaptation training followed by 3 weeks of training (15 sessions; one weekday session per day; \~20 minutes each) using a block design with slow-wave acoustic cueing (1 Hz amplitude-modulated tone; 20 s rest + 40 s cueing per block; 20 blocks/session) Undergo fNIRS recording in all sessions, with ECG recorded in session 1 only (for HR/HRV analyses) Receive matched, guideline-informed cognitive-behavioural therapy (CBT) during the intervention period Complete anxiety-related assessments at baseline, \~1 hour after the final session, and 3 months after treatment, with adverse events monitored throughout the intervention period

The goal of this clinical trial is to test whether real-time fNIRS-BCI neurofeedback targeting the right dorsolateral prefrontal cortex (right DLPFC), using active volitional control during a slow-wave auditory acoustic paradigm, can suppress cardiac sympathetic activity and improve autonomic regulation in right-handed patients with stable coronary heart disease (CHD) and comorbid DSM-5 anxiety. The main questions it aims to answer are: Does real neurofeedback, compared with sham, reduce baseline-corrected heart rate during the auditory stimulation window? Does real neurofeedback, compared with sham, increase HRV spectral power around 0.0167 Hz (1/60 Hz) and produce stronger suppression of right DLPFC activation? Does suppression of right DLPFC activation mediate the effect of group assignment on heart rate? If there is a comparison group: Researchers will compare the real neurofeedback group with the sham (non-contingent) feedback group, which uses identical audio and interface, to determine whether coupling feedback to right DLPFC activity yields autonomic benefits. Participants will: Complete eligibility screening in cardiology and psychiatry and provide informed consent; baseline demographics, medical history, vital signs, and medications are recorded (HAMA/HAMD used for eligibility only). Undergo a 3-day adaptation phase to practice active volitional self-regulation while viewing a real-time energy bar mapped to right DLPFC statistics; adaptation data are not analyzed for outcomes. Attend two formal sessions (Days 4-5), each with 15 blocks of 60 s (20 s rest + 40 s stimulus). The auditory stimulus is a 1 Hz amplitude-modulated pure tone at approximately 60 dB; 10-second white-noise bursts are randomly embedded within the 40-second window. During the stimulation period, participants receive real or sham feedback on right DLPFC activation and act to push the energy bar below an unlabeled threshold line using active volitional strategies. Undergo synchronous fNIRS (HbO) and 3-lead ECG (1,000 Hz) recording throughout; online processing and rendering performance metrics are logged; adverse events are monitored and managed per protocol.

The goal of this clinical trial is to test whether closed-loop fNIRS-BCI neurofeedback(NF) targeting the left dorsolateral prefrontal cortex(DLPFC) can reduce cardiac autonomic arousal, indexed by baseline-corrected heart rate(HR) under cold-induced pain stress, in adults with stable coronary heart disease(CHD) and comorbid anxiety. The main questions it aims to answer are: Does real left DLPFC neurofeedback, compared with sham neurofeedback, lead to a greater reduction in baseline-corrected HR during the cold-induced pain stimulation window? Does real neurofeedback produce stronger volitional upregulation of left DLPFC activation and higher inter-hemispheric synchronisation between left and right DLPFC than sham neurofeedback? Are changes in baseline-corrected HR statistically associated with, and partly mediated by, changes in left DLPFC activation or DLPFC inter-hemispheric synchronisation? What adverse events(AEs) occur during adaptive training and the formal experimental session, and do AE rates differ between the two groups? Researchers will compare a real neurofeedback group with a sham neurofeedback group to determine whether targeting the left DLPFC via closed-loop fNIRS-BCI yields superior modulation of cardiac autonomic responses and prefrontal activation patterns in CHD patients with anxiety. Participants will: undergo cardiac and psychiatric screening to confirm stable CHD, DSM-5 anxiety disorder, and other eligibility criteria; attend three adaptive training sessions(days 1-3) with fNIRS-BCI neurofeedback targeting the left DLPFC, combined with slow-wave auditory stimulation and mild cold-water exposure, while ECG is recorded; on day 4, complete one formal experimental session consisting of 15 blocks of cold-induced pain stimulation and slow-wave auditory stimulation, with simultaneous fNIRS and ECG recording, receiving either real or sham left DLPFC neurofeedback according to randomisation, and continuous monitoring for adverse events.

The goal of this clinical trial is to evaluate whether cold atmospheric plasma (CAP) combined with endovascular intervention can accelerate wound healing and improve safety outcomes in patients aged 18 to 80 years with diabetic foot ulcers (DFUs) complicated by lower extremity arterial occlusion. The main questions it aims to answer are: 1. Does CAP treatment lead to a greater reduction in ulcer area by Week 4 compared to placebo?; 2. Is CAP therapy safe and well-tolerated in patients with DFUs after successful infrapopliteal revascularisation?; Researchers will compare CAP treatment plus standard care to sham CAP (placebo) plus standard care to see if CAP improves wound healing more effectively and reduces adverse local symptoms. Participants will: 1. Receive either active CAP therapy or sham CAP therapy once daily for 10 days following endovascular revascularisation 2. Undergo daily wound assessments for ulcer area, signs of infection, and pain scores 3. Complete quality-of-life questionnaires (EQ-5D and SF-12) at baseline and Week 4 4. Be followed through Week 4 to assess efficacy and safety endpoints

This study is a prospective, randomized, sham-controlled, participant- and assessor-blinded, parallel-group clinical trial designed to evaluate the clinical efficacy, mechanistic effects, and safety of right dorsolateral prefrontal cortex (DLPFC) closed-loop functional near-infrared spectroscopy brain-computer interface (fNIRS-BCI) neurofeedback in patients with high-ischaemic-risk chronic coronary syndrome (CCS) and comorbid anxiety disorder. Participants will be randomly assigned in a 1:1 ratio to active neurofeedback or sham feedback. The intervention consists of 4 weeks of treatment, with 20 sessions in total (1 session per weekday, approximately 20 minutes per session). The primary endpoint is the between-group difference in Hamilton Anxiety Rating Scale (HAMA) score at 3 months after treatment. Secondary endpoints include HAMA score and HAMA response rate at the end of treatment, as well as neurophysiological measures collected during Session 1, including right DLPFC activation, heart rate (HR), and heart rate variability (HRV). Exploratory long-term follow-up will assess cardiovascular and bleeding outcomes through 4 years after randomization.

Critical limb ischemia is the end-stage manifestation of peripheral arterial disease (PAD), frequently presenting as ischemic rest pain, ulceration, or gangrene. Diabetes mellitus is a major risk factor for lower extremity arterial occlusion, with infrapopliteal arteries most commonly affected. Patients with diabetic foot ulcers (DFUs) have a high prevalence of neurovascular complications, poor healing, and elevated amputation and mortality rates. Large-scale cohort studies indicate that five-year survival after amputation in this population is only about 50%, underscoring the need for more effective therapies. Endovascular revascularization has become the first-line treatment for diabetic lower limb ischemia. However, despite successful revascularization, persistent microvascular dysfunction and difficult-to-heal ulcers remain common due to chronic inflammation, impaired angiogenesis, and tissue repair deficits. Current advanced wound dressings provide limited benefit and are often costly. Cold atmospheric plasma (CAP) has emerged as a promising adjunctive therapy, with demonstrated antimicrobial activity-including efficacy against multidrug-resistant organisms-and the ability to promote microcirculation and wound healing. CAP generates reactive oxygen and nitrogen species that disrupt bacterial membranes and may also stimulate tissue regeneration. Preclinical and clinical studies suggest that CAP can accelerate healing in chronic wounds and is well tolerated by patients. Given these advantages, the present study aims to assess the efficacy and safety of CAP combined with endovascular intervention in patients with diabetic foot ulcers and lower extremity arterial occlusion, to inform future clinical application of this novel technology.

Tinea pedis (athlete's foot) is a common and highly contagious fungal infection of the feet. Moderate-to-severe cases present with extensive skin lesions, severe symptoms, frequent recurrences, and increased risk of complications, often proving refractory to conventional topical therapies. Anatomical niches, poor drug penetration, and antifungal resistance make effective management challenging and negatively impact patients' quality of life. Current treatments, including topical and systemic antifungals or physical modalities, are often limited by incomplete efficacy, complexity, or poor adherence. Therefore, more effective and practical treatment options are urgently needed. Atmospheric pressure cold plasma (CAP) is an innovative technology that generates reactive species capable of targeting pathogens while preserving normal tissue. CAP has demonstrated strong antimicrobial effects and promotes wound healing in biomedical research. This study will evaluate the efficacy and safety of CAP in treating moderate-to-severe tinea pedis, aiming to address unmet clinical needs and support future clinical application.

Acne vulgaris is a common, chronic inflammatory skin disease with complex pathogenesis and limited therapeutic options, especially for moderate-to-severe cases. Standard treatments-including topical and oral agents-are often constrained by side effects, antimicrobial resistance, and treatment resistance. Cold atmospheric plasma (CAP), a novel technology that generates reactive oxygen and nitrogen species, has demonstrated antimicrobial and tissue-regenerative properties in dermatology, but robust clinical evidence in acne management remains scarce. Existing data suggest promising efficacy and safety, yet its use in moderate-to-severe acne vulgaris has not been adequately investigated. This study aims to evaluate the efficacy and safety of two self-developed CAP devices as a potential innovative therapy for moderate-to-severe acne vulgaris.