Auditory neuromodulation-based prescription digital therapeutic for insomnia disorder: study protocol for a randomized controlled trial (SERENE).

BACKGROUND: Insomnia affects 10-15% of adults worldwide, significantly impairing quality of life, cognitive function, and work productivity. Current treatments present fundamental trade-offs: cognitive behavioral therapy for insomnia (CBT-I) demonstrates sustained efficacy but requires a prolonged treatment period, specialized therapists, and high patient engagement, while pharmacotherapy provides rapid relief but carries risks of dependence and cognitive impairment that limit long-term use. Existing prescription digital therapeutics (PDTs) address CBT-I's accessibility barriers but inherit its delayed therapeutic onset and adherence challenges. BELL-001 is an auditory neuromodulation-based PDT designed to induce autonomic downregulation through real-time biosignal-responsive acoustic feedback, targeting hyperarousal as a core pathophysiological feature of insomnia. METHODS: This is a multicenter, prospective, randomized, double-blind, sham-controlled, superiority trial designed to evaluate the efficacy and safety of BELL-001 in adults with insomnia. A minimum of 114 participants aged 19-75 years diagnosed with insomnia according to ICD-10 criteria (F51.0 or G47.0) and with an Insomnia Severity Index (ISI) score ≥ 15 will be enrolled from six clinical sites in the Republic of Korea. Eligible participants will be randomly assigned in a 1:1 ratio to either the treatment group using BELL-001 or the control group using a sham device. The primary endpoint is the change in ISI score from baseline to 4 weeks. Secondary endpoints include the response rate (ISI reduction ≥ 6 points), subjective sleep onset latency and wake after sleep onset from sleep diaries, and validated questionnaires assessing sleepiness, fatigue, depression, anxiety, quality of life, and work productivity. Treatment-emergent adverse events will be evaluated for safety analysis. DISCUSSION: The SERENE trial will evaluate whether an auditory neuromodulation-based PDT can provide clinically meaningful imp