Clinical validation of at-home methods of sleep assessment in Rett Syndrome

雷特综合征家庭睡眠评估方法的临床验证

• 批准号: 10435448
• 负责人: SARIKA U PETERS
• 金额: $ 24.33万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10435448
• 关键词: Accelerometer; Adult; Affect; Agreement; Animal Model; Apnea; Assessment tool; Behavior; Biological Markers; Breathing; Caregivers; Child; Circadian Dysregulation; Clinical; Clinical Management; Clinical Research; Clinical Trials; Data; Development; Devices; Disease; Engineering; Enrollment; Environment; Female; Gait abnormality; Galvanic Skin Response; Genes; Gold; Hand; Hand functions; Health; Heart Rate; Home; Home environment; Human; Hyperventilation; Intervention; Language; Link; Measurement; Measures; Methodology; Methods; Methyl-CpG-Binding Protein 2; Movement; Mutation; Neurodevelopmental Disorder; Observer Variation; Outcome; Outcome Measure; Parents; Participant; Pattern Recognition; Personal Satisfaction; Phenotype; Physiological; Physiology; Pilot Projects; Polysomnography; Quality of life; Questionnaires; Reporting; Rett Syndrome; Sampling; Sensitivity and Specificity; Severities; Signal Transduction; Skin Temperature; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Specificity; Stereotyping; Suggestion; Surveys; Symptoms; Technology; Temperature; Time; Validation; Wakefulness; actigraphy; associated symptom; base; clinical outcome measures; clinical trial readiness; clinically relevant; cost; diaries; heart rate variability; improved; instrument; neurogenetics; patient stratification; preclinical study; primary outcome; research study; signal processing; sleep pattern; sleep quality; spelling; standardize measure; wearable device

Project Summary Rett Syndrome (RTT) is a rare, X-linked neurogenetic disorder that affects 1 in 10,000 females and is caused by mutations in the methyl CpG-binding protein 2 gene (MECP2). The classic, or typical, form of RTT is characterized by a period of developmental regression, loss of purposeful hand use, loss of spoken language, gait abnormalities and repetitive, stereotyped hand movements. Also included in the RTT phenotype are sleep problems as well as a variety of symptoms suggestive of autonomic dysregulation including breathing irregularities (e.g. hyperventilation, apnea, breath holding), heart rate variability, temperature dysregulation. Disrupted sleep adversely impacts the quality of life of children with RTT and their parents/caregivers. Clinical trials are underway in RTT, and several include sleep-based outcome measures consisting of caregiver reports from questionnaires and sleep diaries. While these strategies are widely used for studying sleep, they are subject to multiple forms of bias including recall as well as observer bias. Objective, caregiver independent methods of assessing sleep quality are thus required. The gold-standard for objective assessment of sleep is polysomnography (PSG), however this is time-intensive, costly, and impractical for longitudinal assessments that are necessarily part of clinical trials in RTT. Wearable devices are increasingly utilized in sleep research studies because of their ease of use, and ability to capture data for extended periods of time within the home environment. Although our pilot data demonstrates the feasibility of a wearable device to assess sleep in RTT, the sensitivity or specificity of these measurements for sleep quality in RTT is unknown, and they have never been validated against PSG or measures of clinical severity. As such, this project will use state-of-the-art signal processing and pattern recognition methodologies to develop a quantifiable, remote/at-home measure of sleep for use within the context of a clinical trial. We will determine the reliability of a wearable device for sleep quality in RTT against gold-standard PSG. The device being utilized in this study also captures autonomic physiological measurements, so we will additionally determine the change in sensitivity and specificity for sleep quality in RTT when adding these measurements beyond actigraphy alone. Finally, we will determine the convergent validity between sleep quality measured by a wearable device and currently used outcome measures for clinical trials in RTT. Successful completion of these aims could have high impact for RTT because they could be utilized as biomarkers of clinical severity and for the purposes of patient stratification for clinical trials. Finally, these measures could assist in formulating more personalized, targeted interventions aimed at improving sleep quality and caregiver quality of life.

项目摘要 RETT综合征（RTT）是一种罕见的，X连锁的神经遗传疾病，影响10,000名女性，并由。 甲基CpG结合蛋白2基因的突变（MECP2）。 RTT的经典或典型的形式是 以发展性回归的时期，有目的的手用途，口语丧失的特征， 步态异常和重复，定型的手动运动。 RTT表型也包括睡眠 问题以及各种症状提示自主性失调，包括呼吸 不规则性（例如，换气过度，呼吸暂停，呼吸保持），心率变异性，温度失调。 睡眠中断会对RTT及其父母/护理人员儿童的生活质量产生不利影响。临床 RTT的试验正在进行中，其中一些包括由护理人员报告组成的基于睡眠的结果指标 来自问卷和睡眠日记。尽管这些策略被广泛用于研究睡眠，但它们是主题 多种形式的偏见，包括召回和观察者偏见。目的，照顾者独立的方法 因此，需要评估睡眠质量。客观评估睡眠的金标准是 多摄像机（PSG），但是这是时间密集型，昂贵且不切实际的，对于纵向评估 这是RTT临床试验的一部分。可穿戴设备越来越多地用于睡眠研究 研究是因为它们的易用性以及在家庭内长时间捕获数据的能力 环境。尽管我们的飞行员数据证明了可穿戴设备评估RTT睡眠的可行性，但 这些测量对RTT中睡眠质量的敏感性或特异性尚不清楚，而且从未 已针对PSG或临床严重程度的度量进行了验证。因此，该项目将使用最先进的信号 处理和模式识别方法，以开发可量化的远程/家庭睡眠度量 在临床试验的背景下使用。我们将确定可穿戴设备的可靠性以进行睡眠质量 在RTT中针对金色标准的PSG。在本研究中使用的设备还捕获了自主神经生理 测量值，因此我们还将确定RTT中睡眠质量的灵敏度和特异性的变化 仅仅添加这些测量值时，就仅仅是精力射击。最后，我们将确定收敛的有效性 通过可穿戴设备测量的睡眠质量和目前使用的临床试验结果指标 在RTT中。这些目标的成功完成可能会对RTT产生重大影响，因为它们可以用作 临床严重程度的生物标志物以及用于临床试验的患者分层的目的。最后，这些 措施可以帮助制定旨在提高睡眠质量的更个性化的针对性干预措施 和护理人员的生活质量。