Flavored substances for treatment for Obstructive Sleep Apnea

用于治疗阻塞性睡眠呼吸暂停的调味物质

• 批准号: 9199969
• 负责人: christopher hermanson
• 金额: $ 22.5万
• 依托单位: SCIENTIFIC PARTNERS, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-22 至 2017-02-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199969
• 关键词: Adverse event; Affect; Alcohol or Other Drugs use; Anatomy; Anterior; Apnea; Arousal; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chemotactic Factors; Clinical; Continuous Positive Airway Pressure; Cross-Over Studies; Data; Deglutition; Deglutition Disorders; Dental Occlusion; Development; Devices; Diagnosis; Dilator; Disease; Dose; Dose-Rate; Drowsiness; Effectiveness; Endocrine; Equipment; Evaluation; Event; Exercise; Flavoring; Functional disorder; Head and neck structure; Health; Hypoglossal nerve structure; Infusion Pumps; Infusion procedures; Mandible; Measures; Methods; Miniaturization; Morbidity - disease rate; Motor Vehicles; Movement; Muscle; Muscle Tonus; Myocardial Infarction; Newly Diagnosed; Obstructive Sleep Apnea; Operative Surgical Procedures; Oral; Oral cavity; Oropharyngeal; Outcome; Pain; Pathogenesis; Pathway interactions; Patients; Performance; Perioperative; Phase; Polysomnography; Process; Pump; Quality of life; Randomized; Readiness; Research Design; Risk; Role; Safety; Saline; Severities; Sleep; Small Business Innovation Research Grant; Specific qualifier value; System; Taste Perception; Temporomandibular Joint; Tongue; Tooth structure; Vehicle crash; Water; Work; Xylitol; airway obstruction; base; commercialization; cost; design; indexing; man; meetings; minimally invasive; mortality; neuromuscular; neuromuscular stimulation; novel; pressure; prevent; primary outcome; prototype; tongue apex; usability

We propose to develop a novel, minimally invasive treatment for obstructive sleep apnea (OSA) that uses flavored substances as a chemo-attractant to engage the tongue, a process that may be described as chemoactivation. OSA is a disorder of symptomatic, repeated upper airway obstruction during sleep that is associated with substantial cardiovascular morbidity and mortality, endocrine disturbances, daytime somnolence, decreased quality of life, performance deficits, and motor vehicle crashes. 30-40% of OSA patients cannot tolerate first-line treatment (positive airway pressure) and may consider other options, including mandibular repositioning appliances and surgery. Oral appliances and surgery may offer substantial benefit for selected patients, but they carry many risks. The tongue has a pivotal role in OSA pathogenesis and treatment. The benefits of treatment with mandibular repositioning appliances and tongue- directed surgical procedures are based on repositioning and/or reduction in the size of the tongue. Novel tongue-directed therapies utilizing direct neuromuscular stimulation and oropharyngeal exercises have demonstrated encouraging initial results, but these too can be limited by cost, invasiveness, compliance, and/or limited effectiveness. Our strategy for meeting this challenge is an effective, safe, non-invasive device, for use by itself or during CPAP. The RestAssure™ works by engaging the tongue during sleep by using flavored substances to promote tongue movement and swallowing. Using a prototype, first-in-man and pilot data are promising but require further evaluation. For Phase I of this SBIR proposal, we propose to optimize the efficacy of this approach in a study of 30 subjects with newly-diagnosed mild to moderate OSA (based on sleep study, or polysomnogram) and no previous treatment. In addition, we will begin miniaturization and optimization of the pump that will be used on the commercial device. Aim 1: Optimize efficacy and safety with respect to flavor compounds, infusion rates, and dosing intervals. All subjects will undergo overnight polysomnography with an intraoral mouthpiece designed to enable periodic infusion of flavored substances in the anterior oral cavity adjacent to the tongue tip. The primary outcome in assessing each parameter below will be the reduction in OSA severity (apnea-hypopnea index) from the sleep study (polysomnogram). Exploratory outcomes include usability, user acceptance, and changes in arousal index. Adverse events will be measured. 1a) Assess sweet (xylitol) versus salty (saline) versus control (water) flavors. 1b) Assess infusion rates. 1c) Assess duration and interval. Aim 2: Develop a prototype infusion device. The optimization in Aim 1 will utilize an existing portable benchtop infusion pump. For our commercial product, however, we will develop a body-worn infusion device, obviating the need for external tethers or equipment.

我们建议开发一种新的，微创治疗阻塞性睡眠呼吸暂停（OSA） 它使用调味物质作为化学引诱剂来吸引舌头，这个过程可以 被描述为化学活化。阻塞性睡眠呼吸暂停综合征是一种症状性反复发作的上呼吸道疾病， 睡眠期间阻塞，与大量心血管疾病发病率相关， 死亡率、内分泌紊乱、日间嗜睡、生活质量下降、体能 赤字和机动车事故。30-40%的OSA患者不能耐受一线治疗 （气道正压通气），并可能考虑其他选择，包括下颌骨复位 器械和手术。口腔矫正器和手术可能会为选定的患者提供实质性的好处。 病人，但他们有很多风险。舌在阻塞性睡眠呼吸暂停综合征的发病机制中起着关键作用， 治疗下颌复位矫治器和舌- 定向外科手术是基于重新定位和/或减小 舌头.利用直接神经肌肉刺激的新型舌向疗法， 口咽练习已经显示出令人鼓舞的初步结果，但这些也可以是 受到成本、侵入性、顺应性和/或有限有效性的限制。我们的会议策略 这种挑战是一种有效、安全、非侵入性的装置，可单独使用或在CPAP期间使用。的 RestAssure™通过在睡眠期间使用调味物质来吸引舌头， 促进舌头运动和吞咽。使用原型，首先在人和试点数据是 有希望，但需要进一步评估。就这项小型企业改革建议的第一阶段，我们建议 在一项对30名新诊断的轻度至重度抑郁症受试者的研究中， 中度OSA（基于睡眠研究或多导睡眠图），既往无治疗。在 此外，我们将开始小型化和优化的泵，将用于 商业设备。目的1：优化风味化合物的功效和安全性， 输注速率和给药间隔。所有受试者将接受整夜多导睡眠图检查 具有设计成能够将调味物质周期性地注入口腔内的口内吸嘴， 靠近舌尖的口腔前部。评估每一项的主要结果 下面的参数将是睡眠中OSA严重程度（呼吸暂停低通气指数）的降低 多导睡眠图（Polysomnogram）探索性结果包括可用性、用户接受度和变更 唤醒指数将测量不良事件。1a）评估甜味（木糖醇）与咸味 （盐水）对比对照（水）风味剂。1b）评估输注速率。1c）评估期限和 interval.目标2：开发原型输液装置。目标1中的优化将利用 现有的便携式台式输液泵。但是，对于我们的商业产品，我们将 开发一种身体佩戴的输液装置，避免了对外部系绳或设备的需要。