Mechanisms of Change with Early Intervention in Tuberous Sclerosis Complex

结节性硬化症早期干预的变化机制

• 批准号: 10461690
• 负责人: Shafali Spurling Jeste
• 金额: $ 24.63万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461690
• 关键词: Address; Affect; Aftercare; Age; Attenuated; Behavior; Behavior Therapy; Behavioral; Biological Markers; Boston; Brain; Caring; Child; Clinical; Clinical Trials; Cognition; Cognitive; Collaborations; Control Groups; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Early Intervention; Early identification; Electrophysiology (science); Enrollment; Event; Face; Face Processing; Genetic; Genetic Diseases; Goals; Growth; Infant; Intellectual functioning disability; Interdisciplinary Study; Intervention; Intervention Studies; Joints; Language; Lead; Life; Maintenance; Measures; Mediating; Methodology; Mission; Modification; National Institute of Child Health and Human Development; Neurodevelopmental Disability; Neurodevelopmental Disorder; Non-Malignant; Outcome; Outcome Measure; Parents; Pediatric Hospitals; Play; Prenatal Diagnosis; Process; Prospective Studies; Randomized; Regulation; Research; Rest; Site; Social Development; Symptoms; Syndrome; Time; Translational Research; Tuberous sclerosis protein complex; Waiting Lists; autism spectrum disorder; autistic children; behavior change; behavior measurement; behavioral outcome; body system; cognitive neuroscience; comparison group; design; group intervention; high risk; improved; intervention effect; joint attention; neuromechanism; prevent; recruit; relating to nervous system; response; skills; social communication; specific biomarkers; treatment effect; treatment response; visual processing

PROJECT SUMMARY/ABSTRACT Background: Children with Tuberous Sclerosis Complex (TSC) are at high risk for neurodevelopmental disorders, with rates of autism spectrum disorder (ASD) approaching 60%. Prospective studies have found that infants with TSC demonstrate delays in social communication skills in the first year of life. However, to date no studies have investigated whether early behavioral intervention can improve social communication skills in infants with TSC. Objectives: The overarching goal of the study is to determine if social communication function can be improved in infants with TSC with a targeted, short-term behavioral intervention called JASPER (Joint Attention, Symbolic Play, Engagement, Regulation), and to enrich traditional outcome measures by combining behavioral measures with electrophysiological (EEG) biomarkers of social communication. These biomarkers can capture subtle changes in brain development that may reflect responses to treatment prior to an overt behavioral change, particularly relevant for children with significantly delayed development, and they can inform the neural mechanisms underlying the behavioral changes found with intervention. Hypothesis: It is expected that, compared to a wait list control group, infants receiving the JASPER intervention will demonstrate greater gains in social communication skills, with changes captured both behaviorally and electrophysiologically. Methodology: A total of 60 infants with TSC ages 12-36 months will be recruited across two sites with an established collaboration in TSC research, UCLA and Boston Children's Hospital, with each infant randomized to treatment or wait list control group. The wait list control design allows all infants to receive intervention while still maintaining a non-treatment comparison group. Treatment will consist of 12 weeks of weekly intervention sessions. Assessments (clinical, behavioral and EEG) will be performed before treatment, after treatment, 3 months after completion, and then 12 months after completion. Controls will undergo assessments at the same time points, and then will start intervention at month 6. Assessments will include behavioral measures of social communication skills, cognition, language and adaptive function, and EEG measure of resting state brain activity, visual and face processing. Impact: Early intervention improves cognitive and behavioral outcomes in ASD, yet no studies have investigated the effects of targeted, early behavioral intervention in infants with TSC. Evidence of efficacy of early intervention will justify its value for all infants with TSC, improving developmental outcomes and attenuating symptoms that lead to the diagnosis of neurodevelopmental disabilities in TSC. Moreover, this study holds relevance for intervention research across neurodevelopmental disorders through its integration of EEG biomarkers with behavioral measures, as such methodology may more readily capture the effects of treatment in pre-verbal and developmentally delayed infants.

项目摘要/摘要 背景：儿童结节性硬化症(TSC)是神经发育的高危人群 自闭症谱系障碍(ASD)的比率接近60%。前瞻性研究发现， 患有TSC的婴儿在出生的第一年表现出社交技能的延迟。然而，到目前为止，没有 研究调查了早期行为干预是否可以提高患者的社会沟通技能 患有TSC的婴儿。目标：这项研究的首要目标是确定社会沟通是否 通过一种有针对性的短期行为干预，TSC婴儿的功能可以得到改善 Jasper(共同关注、象征性游戏、参与、调节)，并丰富传统结果 行为测量与社会电生理(EEG)生物标记物相结合的措施 沟通。这些生物标志物可以捕捉大脑发育的细微变化，这些变化可能反映 在明显的行为改变之前对治疗的反应，特别是与显著 延缓发育，他们可以告知所发现的行为变化背后的神经机制 通过干预。假设：与等待名单对照组相比，预计接受 贾斯珀的干预将显示出社交沟通技能的更大收获，这两个方面的变化都会被捕捉到 从行为和电生理上来说。方法：共有60名12-36个月的TSC婴儿将 在加州大学洛杉矶分校和波士顿儿童学院这两个在TSC研究方面建立了合作关系的网站上招聘 入院时，将每个婴儿随机分为治疗组或等候名单对照组。等待列表控件设计允许 所有婴儿均接受干预，同时仍维持非治疗对照组。治疗将会 包括为期12周的每周干预会议。评估(临床、行为和脑电)将是 分别于治疗前、治疗后、完成后3个月、完成后12个月进行。 控制将在相同的时间点接受评估，然后将在6个月开始干预。 评估将包括社交技能、认知、语言和 适应功能，以及静息状态脑活动、视觉和面部处理的脑电测量。影响：早期 干预改善了自闭症患者的认知和行为结果，但还没有研究调查其影响 对患有TSC的婴儿进行有针对性的早期行为干预。早期干预的有效性证据将 证明其对所有患有TSC的婴儿的价值，改善发育结果并缓解症状 导致在TSC中诊断为神经发育障碍。此外，这项研究与 脑电生物标记物与神经发育障碍相结合的神经发育障碍干预研究 行为测量，因为这样的方法论可能更容易捕捉到治疗的效果在言语前 和发育迟缓的婴儿。