Closed-loop phase-locked auditory stimulation system at home enhance slow wave sleep for patients with chronic insomnia: A randomized, placebo-controlled trial

Background Neuromodulation is a promising therapeutic alternative for insomnia. We aimed to explore the efficacy and safety of closed-loop phase-locked auditory stimulation (PLAS) system at home in patients with chronic insomnia. Methods A sham-controlled, double-blinded, randomized study applying a closed-loop PLAS system was conducted in patients with chronic insomnia. Recruitment of eligible patients will be on a 1:1:1 basis of randomizing into randomized into an experimental group (EG, a pink noise when the slow wave of sleep reaches its peak), a sham group (SG, a powdered noise that was played at any time in the slow sleep cycles), or a control group (CG, not exposed to the noise). A 5-day intervention was performed after baseline data collection. Participants were required to wear the device every night before bed and remove from the head upon waking up the next morning. The primary outcome measures are sleep quality, and secondary outcome points were mainly assessed by the questionnaires scale that sleep, mental, and cognitive-related assessment. MNE package and custom Python scripts were utilized for pre-processing and analysis of the EEG data and SPSS was used for statistical analysis. Results Thirty-seven patients were recruited for this study, of whom 36 completed the experiment after being randomized. Twelve patients were randomly allocated to each of the EG, SG, and CG. Significant enhancements in the slow wave and theta bands were observed in the stimulation group compared to both the SG and CG (p < 0.05). The stimulating group experienced significantly longer NREM3/4 and REM times compared to the SG or CG (p < 0.05). For the Clinical Global Impression, the score of global improvement is 2.31±1.38 and efficacy index is 2.35±1.01 in STIM group, which indicates that the treatment is effective and safe. Additionally, we analyzed changes in the Montreal Cognitive Assessment, Symbol Digit Modalities Test, Hamilton Depression Scale, and Hamilton Anxiety Scale before and after the intervention. No significant differences were found in cognitive and mental scores among the groups. Conclusion Our results indicate that PLAS has the capacity to enhance slow wave sleep in patients with chronic insomnia, which suggest new possibilities for using PLAS as a low-cost, home-based intervention to improve sleep for insomnia patients, without cognitive and emotional side effects.