Closed-Loop and Open-Loop Acoustic Stimulation During Sleep to Investigate and Modulate Disorders of Arousal in Children and Adults
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of DoA Episodes During the Stimulation Night Compared With the No-Stimulation Night
研究概览
简要总结
Disorders of Arousal (DoA)-such as sleepwalking, sleep terrors, and confusional arousals-are common sleep problems that happen during deep, non-dreaming sleep. Researchers do not fully understand what triggers these episodes or how to influence them.
This study tests whether playing soft sounds during sleep can help researchers learn more about, and possibly induce or modulate, these episodes under safe, supervised conditions. Participants with DoA will spend two nights in the sleep laboratory, with painless sensors placed on the scalp and body (similar to a regular sleep study). On one night, no sound is played. On the other night, soft sounds are played during deep sleep. The order of the two nights is decided randomly for each participant.
A small group of healthy volunteers without DoA will also take part, undergoing a single night with sound stimulation, to help researchers understand whether the sounds affect everyone the same way or specifically trigger episodes in people with DoA.
A subgroup of participants with DoA will also take part in a later, exploratory step in which the sound is triggered automatically, in real time, based on brain activity patterns.
The sounds used are very quiet, similar in volume to normal conversation, and stimulation is stopped right away if a participant shows any discomfort. The goal of this research is to better understand what triggers Disorders of Arousal, and to test whether sound-based stimulation could one day help study or manage this condition.
详细描述
Disorders of Arousal (DoA)-including sleepwalking, sleep terrors, and confusional arousals-are NREM parasomnias whose underlying neurophysiological triggers remain poorly understood. A growing body of evidence suggests that DoA episodes do not emerge randomly from sleep but arise from identifiable pre-episode EEG states characterized by increased slow-wave activity and reduced cortical activation, consistent with a transient state of arousal instability. Closed-loop acoustic stimulation (CLAS) is an established, non-invasive method for probing and modulating NREM sleep physiology, but has not previously been applied in the specific context of NREM parasomnias.
This study investigates whether controlled acoustic stimulation, initially delivered with randomized timing and subsequently in a real-time, EEG-triggered closed-loop fashion, can reliably elicit or modulate DoA episodes under supervised laboratory conditions. A small group of healthy volunteers undergoes a single stimulation night to estimate the specificity of stimulation-elicited motor responses, helping distinguish genuine DoA vulnerability from a non-specific arousal response to sound.
The within-subject, randomized-order design in DoA participants allows each to serve as their own control, isolating the effect of acoustic stimulation from other sources of night-to-night variability. The exploratory closed-loop sub-study tests the technical feasibility of triggering stimulation based on real-time EEG markers of vulnerability, representing a first step toward future predictive or modulation-based approaches for this condition.
This study is part of a broader research programme on the neurobiological characterization of Disorders of Arousal; related observational components (including neuroimaging, neuropsychological assessment, and home monitoring) are registered separately.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For participants with Disorders of Arousal (DoA):
- •Diagnosis of a Disorder of Arousal (sleepwalking, sleep terror, or confusional arousal) per ICSD-3 criteria, confirmed by video-polysomnography or by clinical diagnosis plus a positive Arousal Disorders Questionnaire (ADQ) and compatible history
- •Age 6-17 years (paediatric) or 18-60 years (adult) at enrollment
- •At least one documented episode in the 4 weeks (paediatric) or 6 months (adult) prior to enrollment
- •Ability to understand and complete study materials in Italian
- •Written informed consent (and age-appropriate assent for minors, per Swiss Human Research Act Art. 22-23)
- •For healthy volunteers:
- •No documented sleep disorder, confirmed by clinical interview, questionnaires, or prior instrumental examination
- •Age- and sex-matched to the paediatric DoA group
- •No clinically significant psychiatric or neurological history
- •Written informed consent and age-appropriate assent
排除标准
- •(all participants):
- •Epilepsy or other major neurological disorder
- •Comorbid REM sleep behavior disorder or other REM parasomnia
- •Current psychopharmacological or psychotropic medication (except melatonin ≤2 mg)
- •Neurodevelopmental disorder precluding protocol collaboration (paediatric participants)
- •Clinically relevant sleep-disordered breathing (Apnea-Hypopnea Index >5 events/hour)
- •Clinically significant hearing deficit
- •Significant sleep deprivation in the 48 hours prior to laboratory recording
- •Pregnancy (adult participants)
- •Inadequate EEG recording quality (>40% artifact channels or epochs) - applied at the session level
研究组 & 干预措施
DoA - No-Stimulation Night (Baseline)
Participants with DoA (N=55) undergo overnight high-density EEG and video-polysomnography with no acoustic stimulation. Within-subject baseline condition; order relative to Arm 2 is randomized per participant.
DoA - Acoustic Stimulation Night
The same DoA participants (N=55) undergo overnight high-density EEG and video-polysomnography with low-intensity open-loop acoustic stimulation delivered during slow-wave sleep; order relative to Arm 1 is randomized per participant. A subset of 10 participants additionally undergoes a later, exploratory real-time closed-loop stimulation sub-phase.
干预措施: Closed-Loop/Open-Loop Acoustic Stimulation (CLAS) (Device)
Healthy Control - Single Stimulation Night
A separate group of healthy participants (N=5) undergoes a single overnight high-density EEG and video-polysomnography recording including open-loop acoustic stimulation during slow-wave sleep, to estimate the specificity of stimulation-elicited motor responses relative to the DoA group.
干预措施: Closed-Loop/Open-Loop Acoustic Stimulation (CLAS) (Device)
结局指标
主要结局
Number of DoA Episodes During the Stimulation Night Compared With the No-Stimulation Night
时间窗: Assessed during the two laboratory overnight recordings (no-stimulation night and stimulation night), at least 48 hours apart, up to 6 weeks
Number of video-polysomnographically confirmed Disorders of Arousal (DoA) episodes (sleepwalking, sleep terror, or confusional arousal), compared within-subject between the stimulation night and the no-stimulation (baseline) night.
次要结局
- Duration of DoA Episodes (Seconds): Stimulation Night vs. No-Stimulation Night(Assessed during the two laboratory overnight recordings (no-stimulation night and stimulation night), at least 48 hours apart, up to 6 weeks.)
- Proportion of Slow-Wave Sleep Epochs With Successful Stimulation Trigger (Percentage)(Assessed during the stimulation-night overnight recording, up to 6 weeks.)
- Visual Analogue Scale (VAS) Rating of Perceived Discomfort Related to Acoustic Stimulation(Assessed the morning following the stimulation night, up to 6 weeks.)
- Arousal Index (EEG Arousals per Hour of Sleep): Stimulation Night vs. No-Stimulation Night(Assessed during both laboratory overnight recordings (no-stimulation night and stimulation night), up to 6 weeks.)
- Sleep Efficiency (Percentage): Stimulation Night vs. No-Stimulation Night(Assessed during both laboratory overnight recordings (no-stimulation night and stimulation night), up to 6 weeks.)
研究者
Anna Castelnovo
Senior Physician / Research Group Leader
Neurocenter of Southern Switzerland