Clinical Investigation to Observe the Long-term Safety and Efficacy of the Digital Medical Device 'BELL-001' in Patients Diagnosed With Insomnia

Insomnia is a highly prevalent sleep disorder characterized by persistent difficulty with initiating or maintaining sleep, accompanied by daytime impairment such as fatigue, reduced concentration, mood disturbance, and decreased overall functioning. Despite the availability of pharmacologic options and behavioral approaches such as cognitive behavioral therapy for insomnia (CBT-I), many patients experience limited access, inadequate treatment response, concerns about long-term medication dependence, or poor adherence to structured behavioral interventions. As a result, there remains a significant clinical need for safe, accessible, non-pharmacological therapies that can effectively address the underlying physiological and psychological factors contributing to insomnia.

BELL-001 is a novel digital therapeutic device designed to modulate pre-sleep physiological arousal through personalized auditory stimulation synchronized to an individual's respiratory rhythm. Pre-sleep hyperarousal, including elevated autonomic activation and persistent cognitive and somatic tension, is recognized as a central mechanism in chronic insomnia. BELL-001 analyzes the user's natural breathing pattern through the smartphone microphone and generates real-time auditory feedback aligned with the respiratory phase. This feedback aims to stabilize breathing rhythms, promote parasympathetic activation, reduce sympathetic hyperarousal, and facilitate the transition from wakefulness to sleep. The therapeutic approach is grounded in neurophysiological principles related to interoception, vagal tone modulation, and auditory-respiratory entrainment. Preliminary feasibility and pilot results, including studies conducted at Seoul National University Hospital and Harvard-affiliated centers, suggest that BELL-001 may shorten sleep latency, improve subjective sleep quality, and modulate autonomic markers such as heart rate variability (HRV).

This study is designed as a multicenter, single-arm, prospective clinical trial to observe the long-term safety and effectiveness of the digital medical device BELL-001 in patients diagnosed with insomnia. The study is conducted at three tertiary hospitals in Korea under Good Clinical Practice (GCP) and institutional review board (IRB) oversight. A total of 40 participants will be enrolled, with competitive enrollment across all sites. Participants who meet eligibility criteria based on clinical diagnosis, screening interviews, and baseline assessments will receive BELL-001.

The treatment duration is 12 weeks. Participants will be instructed to use the assigned device during their pre-sleep routine each night. Throughout the study, standardized questionnaires and validated patient-reported outcomes will be administered to assess insomnia severity, depression, anxiety, and work productivity. The outcome measures include changes in the Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Work Productivity and Activity Impairment Questionnaire (WPAI) at 4, 8, and 12 weeks compared to baseline; changes in Total Sleep Time (TST), Sleep Onset Latency (SOL), Wake After Sleep Onset (WASO), and sleep stage ratios measured via Nearable Device at 4, 8, and 12 weeks; and changes in subjective Sleep Latency (sSL), subjective Sleep Quality (sSQ), subjective Wake After Sleep Onset (sWASO), subjective number of awakenings after sleep onset, subjective Sleep Efficiency (sSE), and subjective Total Sleep Time (sTST) assessed through sleep diaries at 4, 8, and 12 weeks compared to baseline. Safety will be evaluated over the 12-week period. Additional outcome measures will include assessment of compliance and satisfaction.

Safety will be continuously evaluated throughout the study by monitoring adverse events, device-related events, and any clinically significant findings at each visit. Given the low-risk nature of the intervention - a non-invasive, non-pharmacological, software-based digital therapeutic device - serious safety concerns are not anticipated. Nonetheless, all participating sites will adhere to rigorous reporting standards, and all safety information will be reviewed by the investigators and IRBs. No independent Data Monitoring Committee (DMC) is planned due to the low-risk profile of the intervention and the presence of established safety oversight mechanisms.

All data will be collected in compliance with GCP and stored in validated electronic case report forms (eCRFs). Statistical analyses will be conducted according to a predefined statistical analysis plan, with the primary analysis based on the full analysis set.

Inclusion criteria

• Diagnosed with ICD-11 nonorganic insomnia (F51.0) or sleep initiation and maintenance disorder (insomnia, G47.0)
• Insomnia Severity Index (ISI) score ≥ 15
• Adults aged 19 to 75 years
• Capable of using a smartphone or tablet and has access to a stable internet connection
• Willing to provide written informed consent voluntarily and able to comply with all study procedures
• Agrees not to initiate any other insomnia treatment other than cognitive behavioral therapy for insomnia during the trial
• Has completed sleep diary entries for at least 3 out of 7 days from the day after the screening visit through the day of the baseline visit (Visit 2)
• At the baseline visit (Visit 2), sleep diary data from the preceding 7 days confirms at least 3 nights with a sleep onset latency of 30 minutes or more, or wake after sleep onset of 60 minutes or more

Exclusion criteria

• Individuals with severe psychiatric disorders, including major depressive disorder
• Individuals diagnosed with or suspected of having insomnia comorbid with narcolepsy (G47.4), obstructive sleep apnea (G47.30), restless legs syndrome (G25.81), periodic limb movement disorder (G47.61), or REM sleep behavior disorder (G47.52) per ICD-10-CM codes
• Individuals with active physical illness or unstable medical conditions that interfere with activities of daily living, including congestive heart failure, chronic obstructive pulmonary disease (COPD), acute pain, cerebrovascular disease (e.g., stroke), or neurodegenerative disorders (e.g., dementia, multiple sclerosis)
• Individuals whose insomnia symptoms are considered to be caused or exacerbated by the physiological effects of medications (prescription drugs or substances of abuse) or alcohol
• Individuals deemed by the investigator to be unable to participate in the study due to respiratory conditions such as asthma
• Individuals with moderate or greater hearing loss in both ears
• Individuals suspected of sleep medication dependence at the investigator's discretion
• Individuals with a history of change in the type or dosage of sleep medications, antidepressants, anticonvulsants, anxiolytics, or antipsychotics within 4 weeks prior to the baseline visit (Visit 2)
• Individuals currently reporting persistent tinnitus symptoms
• Individuals diagnosed with shift work sleep-wake disorder, or those who experience periodic insomnia or sleep-wake rhythm disturbance due to a work environment requiring repeated circadian readjustment, such as day/night shift rotation or frequent international travel
• Individuals who took PRN (as-needed) sleep medications during the screening period (including the day before Visit 1)
• Individuals who used other investigational drugs or investigational digital medical devices within 3 months prior to Visit 1 I-ndividuals with prior experience using BELL-001
• Individuals deemed inappropriate for participation in the clinical trial by the investigator for any other reason