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.

摘要： 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）， 一线手术治疗效果欠佳。阻塞性睡眠呼吸暂停相关夜间间歇性睡眠呼吸暂停的持续性 低氧血症和不完整的睡眠可能会导致认知障碍，以及肺血管 疾病、心肌功能障碍、生活质量下降和日常功能损害。虽然氧气是 有时在其他OSA治疗失败时使用，其有效性和安全性尚未进行系统研究。 因此，该R61/R33设计用于检验患有DS和中度至重度OSA的个体 将具有安全和有利的反应，低流量氧治疗，由于其直接衰减的效果， 缺氧发作，随后增加的睡眠稳定性和OSA的改善。我们进一步 假设氧气补充将导致神经认知、心脏功能、睡眠 和生活质量。R61阶段将积极参与DS患者家属和我们的多方利益相关者 完善和试行方案和招聘战略的团队，以确保我们满足招聘/留用要求 R33阶段的里程碑，我们生成与患者人群最相关的数据。我们会的 筛查约328名5-17岁的DS和中度至重度OSA儿童， 腺样体切除术，以确定氧气反应，然后随机选择230名儿童接受氧气加保守治疗， 治疗（OXT;使用患者特定剂量给药）或单独保守治疗（CT）（体重 管理，睡眠卫生，鼻扩张器）6个月。试验的主要结果是工作记忆 通过共同主要终点测量，分别评估独立报告和客观测量 功能协调发展的次要结局包括心脏功能和结构、右心室压力、生活质量 和睡眠测量，将在经验丰富的中心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研究中心和已建立的DS中心将参与试验。一 数据协调中心在儿科睡眠试验方面经验丰富，有很强的合作历史， 临床研究中心将实施并监测数据质量控制流程，以解决数据处理的所有阶段。 这项研究将填补一个关键的知识空白，在一个潜在的有效治疗OSA，并提供证据， 支持（或反驳）使用辅助供氧，以及识别可能识别的生理标志物 最有可能从该治疗中获益的患者亚组。