Treatment of Obstructive Sleep Apnea with Personalized Surgery in Children with Down Syndrome (TOPS-DS)

通过个性化手术治疗唐氏综合症儿童阻塞性睡眠呼吸暂停 (TOPS-DS)

• 批准号: 10698151
• 负责人: Derek J Lam
• 金额: $ 124.9万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-07 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10698151
• 关键词: Address; Adult; Affect; Age; Anatomy; Apnea; Birth; Cardiovascular system; Case Series; Child; Childhood; Clinical; Clinical Investigator; Cognitive; Collaborations; Complex; Data; Disease; Down Syndrome; Drowsiness; Drug usage; Endoscopes; Endoscopy; Evaluation; Exclusion; Failure; Future; Health; Intervention; Larynx; Medical; Muscle hypotonia; Nose; Obesity; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Participant; Pattern; Pharmaceutical Preparations; Pharyngeal structure; Physiological; Population; Prevalence; Problem behavior; Procedures; Prospective Studies; Quality of life; Randomized; Randomized, Controlled Trials; Recommendation; Risk Factors; Sampling; Sedation procedure; Site; Sleep; Source; Standardization; Testing; Treatment Protocols; Uncertainty; airway obstruction; comparative effectiveness trial; craniofacial; design; effective therapy; effectiveness testing; executive function; experience; flexibility; improved; improved outcome; indexing; individualized medicine; novel; novel strategies; personalized approach; personalized medicine; pharyngeal patterning; positive airway pressure; precision drugs; randomized trial; randomized, clinical trials; standard care; surgery outcome; tongue root; trial comparing

Project Summary The overall objective of this randomized clinical trial is to test the effectiveness of a novel personalized approach to the surgical treatment of OSA in children with Down syndrome (DS). The estimated prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS) ranges from 31-79%, compared to 1-5% in the general pediatric population. Adenotonsillectomy (AT) is the first line treatment for OSA in children, however, most studies of AT outcomes have excluded children with DS. Limited available evidence demonstrates that 50 to 90% of children with DS have persistent OSA after AT. Hypotonia and unfavorable craniofacial anatomy are commonly cited risk factors for failure of AT, however, there have been few attempts to characterize the pharyngeal anatomy or mechanisms of obstruction in this population. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of obstruction during sedated sleep using a flexible endoscope passed through the nose into the pharynx. Several small case series demonstrate that personalized DISE-directed surgery can be effective in treating OSA in children with DS. Because there have been few prospective studies and no randomized trials comparing different treatment options, there remains uncertainty about the most effective treatment for OSA in children with DS. It is our central hypothesis that a personalized DISE-directed surgical approach in children with DS will be superior to the recommended first line treatment of AT. To test this hypothesis, we propose an unprecedented randomized controlled trial of DISE-directed surgery vs AT in children with Down syndrome ages 2-18 years with the following specific aims: Aim 1: Compare the physiological outcomes of DISE-directed surgery vs AT in children with DS. Hypothesis 1: DISE-directed surgery will result in a greater improvement in the obstructive apnea-hypopnea index (OAHI) compared to the standard AT intervention after 6 months. Aim 2: Compare the clinical outcomes of DISE-directed surgery vs AT in children with DS. Hypothesis 2: DISE-directed surgery will result in a clinically significantly greater improvement in disease- specific QOL (OSA18) compared to the standard AT intervention after 6 months. This comparative effectiveness trial will be the first to directly compare a personalized surgical approach to the standard treatment in children with DS This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT.

项目概要 这项随机临床试验的总体目标是测试新型个性化治疗的有效性 唐氏综合症 (DS) 儿童 OSA 的手术治疗方法。估计患病率 唐氏综合症 (DS) 儿童中阻塞性睡眠呼吸暂停 (OSA) 的比例为 31-79%，而唐氏综合症 (DS) 儿童的比例为 1-5% 在一般儿科人群中。腺样体扁桃体切除术 (AT) 是儿童 OSA 的一线治疗方法， 然而，大多数关于 AT 结局的研究都排除了患有 DS 的儿童。现有证据有限 表明 50% 至 90% 的 DS 儿童在 AT 后仍存在持续性 OSA。 肌张力低下和不利的颅面解剖结构是 AT 失败的常见危险因素， 然而，很少有人尝试描述咽部解剖结构或阻塞机制 在这个人群中。药物诱导睡眠内窥镜 (DISE) 可直接观察部位和模式 镇静睡眠期间使用柔性内窥镜通过鼻子进入咽部以防止阻塞。 几个小病例系列表明，个性化 DISE 导向手术可以有效治疗 DS 儿童的 OSA。因为很少有前瞻性研究，也没有随机试验 比较不同的治疗方案，对于 OSA 最有效的治疗方法仍存在不确定性 患有 DS 的儿童。 我们的中心假设是，针对 DS 儿童的个性化 DISE 导向手术方法将 优于推荐的 AT 一线治疗。为了检验这个假设，我们提出了一个 唐氏综合症儿童 DISE 定向手术与 AT 的史无前例的随机对照试验 年龄 2-18 岁，有以下具体目标： 目标 1：比较 DS 儿童 DISE 导向手术与 AT 的生理结果。 假设 1：DISE 导向的手术将导致阻塞性呼吸暂停低通气的更大改善 6 个月后与标准 AT 干预相比。 目标 2：比较 DS 儿童中 DISE 导向手术与 AT 的临床结果。 假设 2：DISE 导向的手术将在临床上显着改善疾病 - 6 个月后与标准 AT 干预相比的具体生活质量 (OSA18)。 这项比较效果试验将是第一个直接比较个性化手术的试验 DS 儿童的标准治疗方法 这种新方法可能会改善 OSA 结局 减少不必要的 AT 或在 AT 无效后持续性 OSA 二次手术的负担。