Medications for Obstructive Sleep Apnea to Improve Cognition in Children with Down Syndrome (MOSAIC DS)

用于改善唐氏综合症儿童认知功能的阻塞性睡眠呼吸暂停药物 (MOSAIC DS)

• 批准号: 10693799
• 负责人: Daniel Combs
• 金额: $ 32.33万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693799
• 关键词: Adherence; Adolescent; Adult; Apnea; Child; Childhood; Cognition; Data; Down Syndrome; Effectiveness; Growth; Hypoglossal nerve structure; Impaired health; Infant; Muscle hypotonia; Neurocognition; Neurocognitive; Neurocognitive Deficit; Obstructive Sleep Apnea; Outcome; Performance; Pharmaceutical Preparations; Phase; Prevalence; Quality of life; Research; Residual state; Route; Schools; Second Look Surgery; Sleep; Time; Treatment Effectiveness; atomoxetine; efficacious treatment; efficacy evaluation; health related quality of life; high risk; improved; indexing; mosaic; novel; oxybutynin; positive airway pressure; targeted treatment

Children with Down syndrome (DS) are known to be at very high risk for obstructive sleep apnea (OSA), with a prevalence of up to 66%. OSA has been associated with neurocognitive impairment and impaired health- related quality of life (HR-QOL) in children with DS. Current treatments for OSA in children with DS include adenotonsillectomy and positive airway pressure (PAP) therapy. Unfortunately, treatment effectiveness is limited by a high risk of residual OSA after adenotonsillectomy and poor adherence to PAP therapy. OSA is prevalent among children with DS and is associated with neurocognitive impairment and impaired HR-QOL. Targeted therapies are needed to mitigate these negative effects of OSA in children with DS. Airway hypotonia during sleep has been identified as a cause of OSA in children with DS. Consistent with this, OSA treatment aimed at improving airway tone via hypoglossal nerve stimulation appears to be effective in adolescents with DS. However, use of hypoglossal nerve stimulation may be limited in children given that multiple revision surgeries would likely be necessary in younger children to adjust for growth over time. The combination of atomoxetine and oxybutynin (ato-oxy) was shown to improve airway tone during sleep and treat OSA in adults without DS. Given that both drugs are routinely used and well-tolerated in children, we hypothesize that ato- oxy will be an efficacious treatment for OSA in children with DS and will lead to improvement in neurocognition and HR-QOL. Specific aims of this project during the R61 phase include: Aim 1: To evaluate the short- term efficacy of ato-oxy treatment for OSA in children with DS. Aim 2: To evaluate the short-term efficacy of ato-oxy treatment on improving HR-QOL in children with DS and OSA. Specific aims of this project during the R33 phase include: Aim 3: To evaluate the long-term efficacy of ato-oxy treatment for OSA in children with DS. Aim 4: To evaluate the long-term efficacy of ato-oxy treatment on improving HR-QOL in children with DS and OSA. Aim 5: To evaluate the efficacy of ato-oxy treatment on improving neurocognition in children with DS and OSA. If successful, this project would identify a novel treatment for OSA in children with DS, as well as medication-based route to improve cognition in children with DS.

众所周知，患有唐氏综合症（DS）的儿童患有阻塞性睡眠呼吸暂停（OSA）的风险很高 高达66％的患病率。 OSA与神经认知障碍和健康障碍有关 DS儿童的相关生活质量（HR-QOL）。 DS儿童中OSA的当前治疗包括 腺孔切除术和阳性气道压力（PAP）治疗。不幸的是，治疗效果是 受腺孔切除术后残留OSA的高风险限制，对PAP治疗的依从性不佳。 OSA是 DS儿童普遍存在，与神经认知障碍和HR-QOL受损有关。 需要有针对性的疗法来减轻DS儿童OSA的这些负面影响。气道低调 在睡眠期间，已确定为DS儿童的OSA原因。与此一致，OSA处理 旨在通过降压神经刺激改善气道音调似乎有效 DS。但是，鉴于多次修订 年幼的孩子可能需要进行手术以适应随着时间的推移的增长。结合 证明阿托西汀和羟丁素（ATO-OXY）可改善睡眠期间的气道张力，并在成人中治疗OSA 没有DS。鉴于两种药物在儿童中常规使用且耐受性良好，我们假设 Oxy将是DS儿童的OSA的有效治疗方法，并将改善神经认知 和HR-QOL。在R61阶段，该项目的具体目的包括：目标1：评估短期 - ATO氧化对OSA对DS儿童的术语疗效。目标2：评估短期功效 DS和OSA儿童改善HR-QOL的ATO氧化治疗。该项目期间的具体目标 R33阶段包括：目标3：评估儿童ATO氧化治疗的长期疗效 与DS。目标4：评估ATO氧化治疗对改善HR-QOL儿童的长期疗效 DS和OSA。目标5：评估ATO氧化治疗对改善儿童神经认知的功效 DS和OSA。如果成功，该项目将确定对DS儿童的OSA的新颖治疗方法 基于药物的途径，以改善DS儿童的认知。