Randomized Control Trial of oxygen therapy in Children and Adolescents with Down Syndrome and Obstructive Sleep Apnea

唐氏综合症和阻塞性睡眠呼吸暂停儿童和青少年氧疗的随机对照试验

• 批准号: 10518497
• 负责人: Raouf S. Amin
• 金额: $ 284.13万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10518497
• 关键词: 17 year old; Address; Adolescent; Age; Agitation; Air; Algorithms; Anatomy; Apnea; Arousal; Attenuated; Behavior; Cardiac; Caregivers; Characteristics; Child; Childhood; Clinical; Clinical Trials; Continuous Positive Airway Pressure; Data; Data Coordinating Center; Dilator; Dose; Down Syndrome; Enrollment; Ensure; Equipment and supply inventories; Family; Financial compensation; Hippocampus (Brain); Hour; Hypoxemia; Hypoxia; Impaired cognition; Impairment; Individual; Injury; Knowledge; Laboratories; Left; Measures; Methods; Monitor; Muscle; Muscle Tonus; Myocardial; Myocardial dysfunction; Neurocognition; Neurocognitive; Nose; Obesity; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Outcome Measure; Oxygen; Oxygen Therapy Care; Participant; Patients; Performance; Phase; Physiologic intraventricular pressure; Physiological; Physiology; Population; Prefrontal Cortex; Process; Protocols documentation; Quality Control; Quality of life; Randomized; Randomized Controlled Trials; Recording of previous events; Reporting; Right Ventricular Function; Safety; Sampling; Severities; Short-Term Memory; Sleep; Sleep disturbances; Structure; Supervision; Supplementation; Testing; Therapeutic; Time; Titrations; Ventricular Function; Weight maintenance regimen; actigraphy; airway obstruction; arm; clinical research site; cognitive function; craniofacial; data handling; data quality; design; efficacious treatment; executive function; experience; functional disability; health related quality of life; heart function; high risk; improved; indexing; mathematical model; neurocognitive test; normoxia; novel; patient population; patient subsets; pharynx muscle; precision medicine; prevent; primary endpoint; primary outcome; pulmonary arterial pressure; pulmonary vascular disorder; randomized trial; recruit; response; secondary outcome; sleep health; supplemental oxygen

ABSTRACT: A large percentage of children with Down Syndrome (DS) have obstructive sleep apnea (OSA) that is suboptimally treated by first-line surgical interventions. The persistence of OSA-related nightly intermittent hypoxemia and fragmented sleep may contribute to a cognitive impairment, as well as pulmonary vascular disease, myocardial dysfunction, reduced quality of life and daily functional impairment. While oxygen is sometimes used when other OSA therapies fail, its efficacy and safety have not been systematically studied. This R61/R33 is therefore designed to test the hypothesis that individuals with DS and moderate to severe OSA will have a safe and favorable response to low-flow oxygen treatment due to its effects on directly attenuating hypoxic episodes, with subsequent increased ventilatory stability and improvement in OSA. We further hypothesize that oxygen supplementation will lead to improvement in neurocognition, cardiac function, sleep, and quality of life. The R61 phase will actively engage families of patients with DS and our multi-stakeholder team to refine and pilot the protocol and recruitment strategies to ensure that we meet our recruitment/retention milestones in the R33 phase and we generate data most relevant to our patient population. In toto, we will screen approximately 328 children with DS and moderate to severe OSA, 5-17 yrs of age, who failed adenotonsillectomy, to identify oxygen responders, and then randomize 230 children to oxygen plus conservative therapy (OXT; administered using a patient-specific dose) or conservative therapy (CT) alone (weight management, sleep hygiene, nasal dilators) for 6 months. The primary outcome of the trial is working memory measured by co-primary endpoints that respectively assess caregiver-reported and objectively measured functions. Secondary outcomes include cardiac function and structure, right ventricular pressure, quality of life and sleep measures that will be collected under the supervision of experienced, central core laboratories. Six clinical sites experienced with pediatric clinical trials and established DS centers will participate in the trial. A Data Coordinating Center experienced with pediatric sleep trials with a strong history of working with these clinical sites will implement and monitor data quality control processes that addresses all stages of data handling. This study will fill a key knowledge gap in a potentially efficacious therapy for OSA, and provide evidence to support (or refute) the use of supplemental oxygen, as well as identify physiological markers to potentially identify patient subgroups most likely to experience benefit from this therapy.

抽象的： 很大一部分患有唐氏综合症 (DS) 的儿童患有阻塞性睡眠呼吸暂停 (OSA)， 一线手术干预治疗效果不佳。 OSA 相关的夜间间歇性持续存在 低氧血症和碎片化睡眠可能会导致认知障碍以及肺血管损伤 疾病、心肌功能障碍、生活质量下降和日常功能障碍。虽然氧气是 有时在其他 OSA 疗法失败时使用，但其疗效和安全性尚未得到系统研究。 因此，该 R61/R33 旨在检验以下假设：患有 DS 和中度至重度 OSA 的个体 由于其对直接衰减的作用，低流量氧气治疗将产生安全且有利的反应 缺氧发作，随后通气稳定性增加并改善 OSA。我们进一步 假设补充氧气会改善神经认知、心脏功能、睡眠、 和生活质量。 R61 阶段将积极吸引 DS 患者家属和我们的多方利益相关者 团队完善和试点协议和招聘策略，以确保我们满足招聘/保留的要求 R33 阶段的里程碑，我们生成与患者群体最相关的数据。总的来说，我们将 对约 328 名 5-17 岁患有 DS 和中度至重度 OSA 的儿童进行了筛查，但均未通过 腺样体扁桃体切除术，以确定氧气反应者，然后将 230 名儿童随机分为氧气加保守治疗 治疗（OXT；使用患者特定剂量进行给药）或单独保守治疗（CT）（体重 管理、睡眠卫生、鼻扩张器）为期 6 个月。试验的主要结果是工作记忆 通过分别评估护理人员报告和客观测量的共同主要终点来测量 功能。次要结局包括心脏功能和结构、右心室压力、生活质量 睡眠测量数据将在经验丰富的中央核心实验室的监督下收集。六 具有儿科临床试验经验的临床中心和已建立的 DS 中心将参与试验。一个 数据协调中心在儿科睡眠试验方面经验丰富，并拥有与这些试验合作的悠久历史 临床中心将实施和监控涉及数据处理所有阶段的数据质量控制流程。 这项研究将填补 OSA 潜在有效疗法的关键知识空白，并为以下方面提供证据： 支持（或反对）使用补充氧气，以及识别生理标志物以潜在地识别 最有可能从这种疗法中受益的患者亚组。