Evaluating Assessment and Medication Treatment of ADHD in Children with Down Syndrome

项目总结 患有唐氏综合症(DS)的儿童注意力缺陷多动的患病率高出3-5倍 儿童多动症(ADHD)比一般发育中的儿童更严重。尽管ADHD的风险更高，但兴奋剂的比率 DS ADHD儿童的药物治疗不成比例地低，尽管兴奋剂是 最有效的ADHD治疗，并被一致推荐用于患有ADHD的儿童 智力障碍(ID)和共病多动症。兴奋剂治疗未得到充分利用的可能原因 DS ADHD包括：1)关于如何准确诊断DS儿童的ADHD的诊断不确定性， 使提供者容易出现“诊断遮蔽”(即，将ADHD归因于ID)；2)没有单一的 临床试验检验兴奋剂治疗DS ADHD儿童的安全性和有效性； 考虑到DS中先天性心脏病或先天缺陷(CHD)的高发病率，对心脏安全的担忧 人口。我们建议进行一项初步研究，以确定DS ADHD的临床特征，从而实现更多 准确的诊断和试点临床试验，为更大规模临床试验的样本量估计提供信息。我们建议 对患有DS ADHD的儿童进行首次随机临床试验，以提供 关于DS ADHD儿童使用兴奋剂的短期和长期安全性和有效性的证据， 无论有无冠心病。100(100)名患有DS ADHD的儿童和70名患有DS但无ADHD的儿童 (DS-ADHD)，所有年龄在6-12岁，年龄、性别和智商匹配的人都将参加。所有170名儿童都参加了 这项研究将完成对ADHD诊断标准的全面评估，以及 行为、认知、学习和功能障碍。DS ADHD组的100名儿童也将 完成一项多阶段随机双盲临床试验，交叉使用安慰剂和长期随访- UP评估兴奋剂治疗ADHD的近、远期疗效和安全性 DS儿童的症状和损害。研究目标将集中在1)确定行为、认知、 将DS-ADHD儿童与DS-ADHD儿童区分开来的学习、和功能障碍； 2)通知较大临床试验的样本量；3)评估兴奋剂的短期和长期安全性 DS ADHD儿童的治疗，特别关注心脏安全；4)确定短期和 刺激性治疗在纠正认知、行为和功能障碍方面的长期疗效 患有多动症的儿童；5)探索调节因素(例如，智商、ADHD亚型、执行功能、 兴奋剂反应和副作用的共病内化障碍。这项研究的结果将 提供急需的诊断和治疗数据，这些数据将直接影响大约 全国范围内有4.5万名患有多动症的儿童。

PROJECT SUMMARY Children with Down syndrome (DS) have a 3-5 times greater prevalence of Attention Deficit Hyperactivity Disorder (ADHD) than typically developing children. Despite this higher risk of ADHD, rates of stimulant medication treatment are disproportionately low in children with DS+ADHD even though stimulants are the most efficacious ADHD treatment and are recommended by consensus guidelines for use in children with intellectual disability (ID) and comorbid ADHD. Possible reasons for under-utilization of stimulant treatment in DS+ADHD include: 1) diagnostic uncertainty regarding how to accurately diagnose ADHD in children with DS, making providers prone to “diagnostic overshadowing” (i.e., attributing ADHD to the ID); 2) there is not a single clinical trial examining the safety and efficacy of stimulant medication in children with DS+ADHD; and 3) concerns about cardiac safety, given the high incidence of congenital heart disease or defects (CHD) in the DS population. We propose a pilot study to define the clinical features of DS+ADHD thereby enabling more accurate diagnosis and a pilot clinical trial to inform sample size estimates for a larger clinical trial. We propose to perform the first randomized clinical trial of stimulant medication in children with DS+ADHD to provide evidence regarding the short and long-term safety and efficacy of stimulant use in children with DS+ADHD, both with and without CHD. One hundred (100) children with DS+ADHD and 70 children with DS and no ADHD (DS-ADHD), all aged 6-12 and matched on age, gender, and IQ, will participate. All 170 children enrolled in the study will complete a comprehensive assessment battery evaluating ADHD diagnostic criteria as well as behavioral, cognitive, academic, and functional impairments. The 100 children in the DS+ADHD group will also complete a multi-phased randomized, double-blind clinical trial with crossover to placebo and long-term follow- up to assess the short- and long-term efficacy and safety of stimulant medications for treating ADHD symptoms and impairment in children with DS. Study aims will focus on 1) Identifying behavioral, cognitive, academic, and functional impairments that differentiate children with DS+ADHD from children with DS-ADHD; 2) Informing sample size of larger clinical trial; 3) Assessing the short- and long-term safety of stimulant treatment in children with DS+ADHD with a specific focus on cardiac safety; 4) Determining the short- and long-term efficacy of stimulant treatment at remediating cognitive, behavioral, and functional impairments in children with DS+ADHD; and 5) Exploring moderators (e.g., IQ, ADHD subtype, executive functioning, comorbid internalizing disorders, CHD) of stimulant response and side effects. Results from this study will provide much needed diagnostic and treatment data that will directly impact the outcomes of the approximately 45,000 children with DS+ADHD nationwide.