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: 10469833
• 负责人: Daniel Combs
• 金额: $ 13.01万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469833
• 关键词: Adherence; Adolescent; Adult; Apnea; Child; Childhood; Cognition; Data; Down Syndrome; Effectiveness; Growth; Hypoglossal nerve structure; Impaired health; Impairment; Infant; Lead; Muscle hypotonia; Neurocognition; Neurocognitive; Neurocognitive Deficit; Obstructive Sleep Apnea; Operative Surgical Procedures; Performance; Pharmaceutical Preparations; Phase; Prevalence; Quality of life; Research; Residual state; Route; Schools; Sleep; Time; Treatment Effectiveness; atomoxetine; base; efficacious treatment; efficacy evaluation; health related quality of life; high risk; improved; indexing; novel; oxybutynin; 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) 的儿童患阻塞性睡眠呼吸暂停 (OSA) 的风险非常高， 患病率高达66%。 OSA 与神经认知障碍和健康受损有关 DS 儿童的相关生活质量（HR-QOL）。目前治疗 DS 儿童 OSA 的方法包括 腺样体扁桃体切除术和气道正压通气（PAP）治疗。不幸的是，治疗效果是 由于腺样体扁桃体切除术后残留 OSA 的高风险以及对 PAP 治疗的依从性差而受到限制。阻塞性睡眠呼吸暂停是 多见于 DS 儿童，与神经认知障碍和 HR-QOL 受损有关。 需要靶向治疗来减轻 OSA 对 DS 儿童的这些负面影响。气道肌张力低下 睡眠期间已被确定为 DS 儿童 OSA 的一个原因。与此相一致的是，OSA 治疗 旨在通过舌下神经刺激改善气道张力，似乎对患有以下疾病的青少年有效 DS。然而，考虑到多次修正，舌下神经刺激在儿童中的使用可能受到限制 年幼的孩子可能需要进行手术，以适应随着时间的推移而生长的情况。的组合 阿托西汀和奥昔布宁 (ato-oxy) 被证明可以改善睡眠期间的气道张力并治疗成人阻塞性睡眠呼吸暂停 (OSA) 没有DS。鉴于这两种药物在儿童中常规使用且耐受性良好，我们假设 吸氧将成为 DS 儿童 OSA 的有效治疗方法，并将改善神经认知 和 HR-QOL。该项目在 R61 阶段的具体目标包括： 目标 1：评估短期 ato-oxy 治疗 DS 儿童 OSA 的长期疗效。目标 2：评估短期疗效 ato-oxy 治疗可改善 DS 和 OSA 儿童的 HR-QOL。本项目期间的具体目标 R33 阶段包括： 目标 3：评估 ato-oxy 治疗儿童 OSA 的长期疗效 与DS。目标 4：评估 ato-oxy 治疗对改善儿童 HR-QOL 的长期疗效 DS 和 OSA。目标 5：评估 ato-oxy 治疗对改善儿童神经认知的功效 DS 和 OSA。如果成功，该项目将找到一种治疗 DS 儿童 OSA 的新方法，以及 以药物为基础的途径来改善 DS 儿童的认知能力。