Sleep Efficacy Randomized Evaluation of a Novel Digital Therapeutic for 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 response, concerns about long-term medication dependence, or difficulty adhering 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 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 or 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 pivotal, multicenter, randomized, double-blind, sham-controlled clinical investigation has been designed to evaluate the efficacy and safety of BELL-001 for improving insomnia symptoms in adults diagnosed with insomnia disorder. The study is conducted at multiple tertiary hospitals in Korea under Good Clinical Practice (GCP) and institutional review board (IRB) oversight. A total of 114 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 be randomly assigned in a 1:1 ratio to the active treatment group (BELL-001) or the sham comparator group. The sham device is designed to closely mimic the visual and functional appearance of the active system but does not deliver personalized respiratory-synchronized auditory feedback, ensuring maintenance of blinding for both participants and investigators.

The treatment duration is four weeks. Participants will be instructed to use the assigned intervention during their pre-sleep routine each night. Throughout the study, standardized questionnaires and validated patient-reported outcomes will be administered to assess insomnia severity, daytime sleepiness, fatigue, mood, anxiety, sleep health, and quality of life. These include the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), PHQ-9, GAD-7, EQ-5D-5L, sleep diaries, and user satisfaction scales. The primary endpoint is the change in ISI score from baseline to Week 4. Secondary endpoints include changes in daytime functioning, sleep diary metrics, mood and anxiety symptoms, fatigue, quality of life, work productivity, and subjective satisfaction with the intervention. Exploratory endpoints may include analysis of symptom trajectories, subgroup patterns, and predictors of treatment response.

Safety will be continuously evaluated throughout the study by monitoring adverse events, device-related events, and any clinically significant findings during follow-up visits. Given the low-risk nature of the intervention-a non-invasive, non-pharmacological, software-based digital therapeutic-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 institutional review boards (IRBs). No independent data monitoring committee is planned due to the low-risk profile of the intervention and the presence of established safety oversight mechanisms.

Randomization and allocation concealment are managed via a centralized system to ensure blinding of participants, investigators, and study staff. 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. The trial is powered to detect a clinically meaningful difference in ISI improvement between active and sham groups. Sensitivity analyses and subgroup analyses will further characterize the robustness of the findings.

The overall aim of this pivotal investigation is to generate definitive clinical evidence supporting the regulatory evaluation and potential approval of BELL-001 as a digital therapeutic medical device for the treatment of insomnia in adults. By rigorously evaluating both symptom improvement and safety outcomes in a randomized, sham-controlled design, this study is expected to establish the therapeutic value of a personalized, physiology-based digital intervention. The results have the potential to advance the field of digital therapeutics, expand accessible options for insomnia management, and contribute to a better understanding of how respiratory-synchronized auditory stimulation may modulate pre-sleep arousal and sleep initiation processes.

Inclusion criteria

• Adults aged 19 to 75 years.
• Clinical diagnosis of insomnia disorder according to ICD-11 criteria (non-organic insomnia or sleep initiation/maintenance disorder).
• Insomnia Severity Index (ISI) score ≥ 15 at screening.
• Reports difficulty initiating or maintaining sleep at least 3 nights per week for ≥ 3 months.
• Willing and able to use a smartphone-based digital therapeutic during the pre-sleep period for 4 weeks.
• Able to provide informed consent and comply with study procedures.

Exclusion criteria

• Other primary sleep disorders (e.g., obstructive sleep apnea, restless legs syndrome, narcolepsy, circadian rhythm sleep-wake disorders).
• Major psychiatric disorders that may interfere with study assessment (e.g., psychotic disorders, bipolar disorder, severe major depressive episode).
• Substance use disorder, including alcohol or hypnotic misuse, within the past 12 months.
• Use of sleep-inducing medications or CNS-active drugs that cannot be stabilized or discontinued per protocol.
• Significant medical or neurological conditions that may affect sleep or study outcomes (e.g., severe cardiovascular, respiratory, or neurological disease).
• Night-shift workers or individuals with irregular sleep-wake schedules.
• Pregnancy or breastfeeding.
• Participation in another interventional clinical study within the past 30 days.
• Any condition judged by the investigator to interfere with study participation, safety, or data validity.