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：联合用药和行为治疗对儿童精神分裂症的影响 ASD和ADHD并存 患有自闭症谱系障碍(ASD)和注意缺陷多动障碍(ADHD)的儿童 结果比那些单独患有ASD或单独患有ADHD的人要差得多。目前，提前生效 尚未开发出考虑ADHD症状存在的治疗方法 患有自闭症的儿童。项目3的首要目标是：(1)评估一种新的早期干预 为患有自闭症和ADHD的幼儿量身定做的模型，从药物上解决ADHD症状 在启动早期行为干预之前；以及(2)确定行为和神经生理学的变化 活动可能是改善患有自闭症和多动症儿童预后的基础。我们将完成 这些目标是通过系统地评估刺激性治疗是否增强父母的疗效- 提供基于早起丹佛模式(P-ESDM)的行为干预。患有自闭症和ADHD的儿童 将随机接受缓释安非他明产品(Adzenys-XR-ODT；AMP)或 在开始早期行为干预之前服用安慰剂。将提供灵活剂量的AMP或安慰剂 30周，在双盲条件下。P-ESDM将由为90人提供的个别家长教练组成 AMP或安慰剂开始服用6周后开始，每周服用2分钟，持续24周。主要结果将是 共同注意启动的频率，这是ASD的一个核心症状，以及社交和交流功能 用Vineland适应行为量表进行评估。我们的主要假设是减少ADHD 在P-ESDM之前和期间的症状将有助于ASD+ADHD儿童最初和持续的注意 对于P-ESDM活动，导致更多地参与P-ESDM并从P-ESDM中获得更大的好处，这反映在更大的 改善联合注意力以及社会和沟通功能。次要目标是确定 用ADHD评定量表评估改善ADHD症状的有效性和耐受性 ADZENYS-XR-ODT在儿童ASD+ADHD中的应用我们还将确定两者之间的关联 联合注意、社交和沟通功能以及ADHD的变化(治疗前后) 社交注意力的症状和变化(通过眼球跟踪生物标记物评估)和持续的社交 与照顾者的参与度(通过对亲子互动的结构化观察进行评估)。最后，我们会 检查结果变化和神经生理指标变化之间的关系 连通性和神经稳定性(脑电一致性和审判间期一致性)和对社会的反应 刺激(事件相关脑电位)。如果兴奋剂和行为学的联合使用有显著的有益效果 治疗对儿童结果的影响已得到证实，项目3将为当前的临床治疗提供重要信息 患有自闭症和多动症的幼儿，这可能会减轻共同疾病的负面影响。 ADHD症状的出现对ASD儿童预后的影响。