Effects of Hypoglossal Nerve Stimulation on Cognition & Language in Down Syndrome

舌下神经刺激对认知的影响

• 批准号: 10470820
• 负责人: CHRISTOPHER J HARTNICK
• 金额: $ 76.08万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10470820
• 关键词: 21 year old; Adolescent; Adult; Age; Apnea; Attention; Blinded; Caregivers; Cessation of life; Child; Childhood; Clinical Trials; Cognition; Continuous Positive Airway Pressure; Data; Developmental Delay Disorders; Disease; Down Syndrome; Ear; Enrollment; Eye; FDA approved; Genetic Diseases; Goals; Hypoglossal nerve structure; Impairment; Implant; Intellectual functioning disability; Intelligence; Language; Language Tests; Lead; Life; Link; Longevity; Masks; Massachusetts; Measures; Motor; Neurocognition; Neurocognitive; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Outcome Measure; Outcome Study; Parents; Patients; Persons; Phase; Phase I Clinical Trials; Pilot Projects; Population; Postoperative Period; Prevalence; Procedures; Pulmonary Heart Disease; Quality of life; Reporting; Research Personnel; Safety; Sample Size; Sampling; Schools; Sensory; Severities; Site; Sleep; Speech; Surveys; Tail; Testing; Tongue; United States; Vocabulary; alternative treatment; base; cardiopulmonary system; executive function; exhaust; implantation; improved; indexing; memory consolidation; neurocognitive test; non-compliance; novel; novel therapeutics; pediatric patients; primary outcome; processing speed; recruit; skills; sleep quality; standard measure; sustained attention; syntax

Project Summary/Abstract Down syndrome (DS) is one of the most common genetic conditions in the United States with a prevalence rate estimated at 6.7 people with DS per 10,000 of the population in 20101 and is characterized by global developmental delays, intellectual disability, and obstructive sleep apnea (OSA),2,3 which may be linked to severe impairments in speech and language domains for those with DS.4 Hypoglossal nerve stimulation (HGS) is a novel therapy for OSA in adults and children.5,6 Since 2015, Massachusetts Eye and Ear (MEEI) has conducted a multi-center FDA-approved Phase 1 clinical trial examining the effects of HGS on children and adolescents ages 10-21 with DS and has shown to diminish OSA. The primary outcome is implant safety while secondary measures are changes in the standard measure of OSA called the Apnea Hypopnea Index. Following qualitative parental reports of speech and language improvement, formal language testing using a procedure called Expressive Language Sampling (ELS) and neurocognitive testing (NCT) were conducted on 5 children children prior to surgery and then 3-6 months post HGS. Results showed an improvement in their IQs, in the diversity of vocabulary and complexity of syntax in spoken language, as well as in several neurocognitive domains. However, despite this promising data, more rigorous testing is needed with a larger sample size to demonstrate the significance of these findings in a rigorous fashion. This proposed study focuses on the effects on neurocognition and expressive language before and after hypoglossal nerve stimulation (HGS) treatment of Obstructive Sleep Apnea (OSA) for 57 children and adolescents who are 10 to 21 years of age. Our aims include: (1) we will test if the treatment of severe OSA with HGS significantly improves the neurocognition of patients with DS. Our hypothesis is that HGS, by improving sleep and thereby facilitating memory consolidation, will result in patients with DS having an improvement of at least 0.5 SD from baseline neurocognitive measures. The primary outcomes of the study will be five neurocognitive measures collected pre-operatively and at 6 months postoperatively: brief attention, sustained attention, processing speed, verbal intelligence, and executive functioning; and (2) we will test if the treatment of severe OSA with HGS significantly improves the expressive language skills (ELS) of patients with DS. Our hypothesis is that HGS, by strengthening the motor tone of the tongue musculature, will result in patients with DS having an improvement of at least 0.5 SD on the ELS measures. The two primary outcomes will be a measure of the diversity of vocabulary and a measure of syntactic complexity, each derived from an ELS narrative, or storytelling procedure. Narrative samples will be collected pre-operatively and then 6 months post-operatively at each site and sent to a central site where blinded investigators will transcribe and analyze the samples of expressive language.

项目概要/摘要 唐氏综合症 (DS) 是美国最常见的遗传病之一 20101 年估计患病率为每 10,000 人中有 6.7 人患有 DS，其特点是 整体发育迟缓、智力障碍和阻塞性睡眠呼吸暂停 (OSA)，2,3 这些可能存在关联 DS.4 患者的言语和语言领域存在严重障碍 舌下神经刺激 (HGS) 是一种治疗成人和儿童 OSA 的新型疗法。5,6 自 2015 年以来， 马萨诸塞州眼耳医院（MEEI）进行了 FDA 批准的多中心 1 期临床试验 研究 HGS 对患有 DS 的 10-21 岁儿童和青少年的影响，结果显示其影响有所减弱 OSA。主要结果是种植体安全性，而次要指标是标准指标的变化 OSA 称为呼吸暂停低通气指数。遵循家长关于言语和语言的定性报告 改进，使用称为表达语言采样（ELS）的程序进行正式语言测试，以及 对 5 名儿童在手术前和手术后 3-6 个月进行了神经认知测试 (NCT) HGS。结果显示，他们的智商、词汇多样性和语法复杂性都有所提高 口语以及几个神经认知领域。然而，尽管有这些充满希望的数据， 需要更大的样本量进行严格的测试，以证明这些发现在 严谨时尚。这项拟议的研究重点是对神经认知和表达语言的影响 舌下神经刺激 (HGS) 治疗阻塞性睡眠呼吸暂停 (OSA) 57 例前后 10至21岁的儿童和青少年。我们的目标包括：（1）我们将测试治疗是否 严重 OSA 合并 HGS 显着改善 DS 患者的神经认知。我们的假设是 HGS 通过改善睡眠从而促进记忆巩固，将导致 DS 患者 与基线神经认知测量相比至少有 0.5 SD 的改善。主要结果 该研究将在术前和术后 6 个月时收集五项神经认知测量：简要 注意力、持续注意力、处理速度、语言智力和执行功能； (2) 我们将 测试 HGS 治疗严重 OSA 是否显着提高语言表达能力 DS 患者的 (ELS)。我们的假设是 HGS 通过加强舌头的运动音调 肌肉组织，将导致 DS 患者的 ELS 测量至少改善 0.5 SD。 两个主要结果将是词汇多样性的衡量和句法的衡量 复杂性，每一个都源自 ELS 叙述或讲故事的程序。将收集叙述样本 术前和术后 6 个月在每个部位进行检查，并发送至盲法中心部位 调查人员将转录并分析表达语言的样本。