Impact of combined medication and behavioral treatment in young children with comorbid ASD and ADHD

联合药物治疗和行为治疗对患有 ASD 和 ADHD 共病的幼儿的影响

• 批准号: 10227713
• 负责人: Linmarie Sikich
• 金额: $ 50.59万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-07 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227713
• 关键词: Adaptive Behaviors; Address; Aftercare; Amphetamines; Attention; Attention deficit hyperactivity disorder; Behavior Therapy; Behavioral; Biological Markers; Brain; Caregivers; Child; Clinical Treatment; Communication; Detection; Development; Diagnosis; Dose; Double-Blind Method; Early Diagnosis; Early Intervention; Early identification; Early treatment; Electroencephalography; Event; Exhibits; Eye; Frequencies; Goals; Individual; Measures; Modeling; Outcome; Parent-Child Relations; Parents; Pattern; Pharmaceutical Preparations; Pharmacology; Phase; Placebos; Problem behavior; Randomized; Randomized Controlled Trials; Research; Social Interaction; Socialization; Stimulus; Structure; Symptoms; Treatment outcome; autism spectrum disorder; autistic children; base; behavioral outcome; comorbidity; effective therapy; efficacy evaluation; flexibility; functional outcomes; gaze; improved; improved outcome; individuals with autism spectrum disorder; joint attention; neuromechanism; neurophysiology; novel; peer; primary outcome; programs; reduce symptoms; relating to nervous system; response; social; social attention; social communication; social engagement; sustained attention; treatment response; visual tracking

ABSTRACT - Project 3: Impact of combined medication and behavioral treatment in young children with comorbid ASD and ADHD Children with comorbid autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have significantly worse outcomes than those with either ASD alone or ADHD alone. Currently, effective early treatment approaches that take into account the presence of ADHD symptoms have not been developed for young children with ASD. The overarching goals of Project 3 are to (1) evaluate a novel early intervention model personalized for young children with ASD+ADHD that pharmacologically addresses ADHD symptoms prior to initiating early behavioral intervention; and (2) identify changes in behavioral and neurophysiological activity that may underlie improved outcomes in children with comorbid ASD and ADHD. We will accomplish these goals by systematically evaluating whether stimulant treatment augments the efficacy of a parent- delivered behavioral intervention based on the Early Start Denver Model (P-ESDM). Children with ASD+ADHD will be randomized to receive either an extended release amphetamine product (Adzenys-XR-ODT; AMP) or placebo prior to initiating early behavioral intervention. The flexibly dosed AMP or placebo will be provided for 30 weeks under double-blind conditions. P-ESDM will consist of individual parent coaching provided for 90 minutes weekly for 24 weeks beginning six weeks after AMP or placebo is initiated. The primary outcomes will be frequency of joint attention initiations, a core ASD symptom, and social and communicative functioning assessed with the Vineland Adaptive Behavior Scales. Our primary hypothesis is that reducing ADHD symptoms prior to and during P-ESDM will facilitate initial and sustained attention of children with ASD+ADHD to P-ESDM activities, leading to more engagement in and greater benefit from P-ESDM, reflected in greater improvements in joint attention and social and communicative functioning. Secondary aims are to determine the efficacy for improving ADHD symptoms, assessed with the ADHD-Rating Scale, and tolerability of Adzenys-XR-ODT in young children with ASD+ADHD. We will also determine the association between changes (pre- and post-treatment) in joint attention, social and communicative functioning, and ADHD symptoms and changes in social attention (assessed via an eye-tracking biomarker) and sustained social engagement with caregiver (assessed via structured observations of parent-child interaction). Finally, we will examine the association between changes in outcomes and changes in neurophysiological measures of neural connectivity and neural stability (EEG coherence and intertrial phase coherence) and responsiveness to social stimuli (event-related brain potentials). If significant beneficial effects of combined stimulant and behavioral treatment on children's outcomes are demonstrated, Project 3 will significantly inform current clinical treatment of young children with co-morbid ASD and ADHD, which could potentially mitigate the negative impact of co- occurring ADHD symptoms on outcomes of children with ASD.

摘要 - 项目3：幼儿的药物和行为治疗联合治疗的影响 合并ASD和ADHD 合并症自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）的儿童 与单独使用ASD或单独使用ASD的人相比，结果明显差。目前，有效 考虑到存在多动症症状存在的治疗方法尚未开发 ASD的年幼孩子。项目3的总体目标是（1）评估新颖的早期干预 针对患有ASD+ADHD的年轻儿童的模型，药理学可以解决多动症症状 在开始早期行为干预之前； （2）确定行为和神经生理学的变化 在合并ASD和ADHD的儿童中，可能改善了结果的活动。我们将完成 通过系统地评估刺激治疗是否会增强父母的功效，这些目标是否会增强 基于早期起始丹佛模型（P-ESDM）提供了行为干预。患有ASD+ADHD的孩子 将被随机分配以接收扩展释放苯丙胺产品（Adzenys-XR-ODT； AMP）或 安慰剂在开始早期行为干预之前。将提供灵活的剂量放大器或安慰剂 在双盲条件下30周。 P-ESDM将包括提供90的个人父母教练 每周启动放大器或安慰剂后六周，每周几分钟开始24周。主要结果将 成为联合注意力开始的频率，核心ASD症状以及社会和交流功能 用Vineland自适应行为量表进行评估。我们的主要假设是减少多动症 P-ESDM之前和期间的症状将促进ASD+ADHD儿童的初始和持续关注 进行P-ESDM活动，导致P-ESDM的更多参与和更大的收益，反映在更大的 共同关注以及社会和交流功能的改善。次要目标是确定 改善ADHD症状的功效，以ADHD评分量表进行评估以及可耐受性 ASD+ADHD的幼儿Adzenys-XR-ODT。我们还将确定 共同关注，社会和沟通功能以及多动症的变化（治疗前后）的变化（治疗前后） 症状和社会关注的变化（通过引人注目的生物标志物评估）并持续社交 与护理人员的互动（通过亲子互动的结构化观察评估）。最后，我们会的 检查结局变化与神经生理测量的变化之间的关联 连通性和神经稳定性（脑电图连贯性和内部阶段连贯性）和对社会的反应 刺激（事件相关的大脑电位）。如果联合刺激和行为的重大有益作用 证明了有关儿童结果的治疗 与Coborbid ASD和ADHD的幼儿有关，这可能会减轻共同的负面影响 在ASD儿童的结局上出现多动症症状。