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

项目摘要 唐氏综合症（DS）儿童的注意力缺陷多动症患病率是其他儿童的3-5倍。 注意力缺陷多动症（ADHD）比一般发育中的儿童。尽管患多动症的风险较高，但兴奋剂的使用率 药物治疗在DS+ADHD儿童中不成比例地低，尽管兴奋剂是 最有效的ADHD治疗，并建议共识指南用于儿童 智力残疾（ID）和共病ADHD。兴奋剂治疗利用不足的可能原因 DS+ADHD包括：1）关于如何准确诊断DS儿童ADHD的诊断不确定性， 使得提供者倾向于“诊断遮蔽”（即，（2）没有一个人（2）没有一个人 检查DS+ADHD儿童中兴奋剂药物的安全性和有效性的临床试验;以及3） 考虑到DS中先天性心脏病或缺陷（CHD）的高发病率，对心脏安全性的担忧 人口我们提出了一项试点研究，以确定DS+ADHD的临床特征，从而使更多的 准确的诊断和试点临床试验，为更大规模的临床试验提供样本量估计。我们提出 在DS+ADHD儿童中进行第一次刺激性药物的随机临床试验， 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， 无论是否患有冠心病。100例DS+ADHD儿童和70例DS但无ADHD儿童 （DS-ADHD），所有6-12岁，年龄，性别和智商匹配，将参加。所有170名儿童都参加了 这项研究将完成一个全面的评估电池评估多动症的诊断标准，以及 行为、认知、学业和功能障碍。DS+ADHD组的100名儿童也将 完成一项多期随机、双盲临床试验，交叉至安慰剂并长期随访- 评估刺激性药物治疗ADHD的短期和长期疗效和安全性 DS儿童的症状和损害。研究目标将集中在1）识别行为，认知， 学习和功能障碍，将DS+ADHD儿童与DS-ADHD儿童区分开来; 2)为大型临床试验提供样本量信息; 3）评估兴奋剂的短期和长期安全性 治疗患有DS+ADHD的儿童，特别关注心脏安全性; 4）确定短期和长期治疗方案， 兴奋剂治疗对认知、行为和功能障碍的长期疗效 患有DS+ADHD的儿童;以及5）探索调节者（例如，智商，多动症亚型，执行功能， 共病内化障碍，CHD）的刺激反应和副作用。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 全国有45,000名DS+ADHD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.