Amitriptyline and Topiramate in the Prevention of Childhood Migraine: DCC

描述（由申请人提供）：偏头痛影响着美国600多万儿童和青少年，其中大多数人在成年后继续经历偏头痛。在美国，偏头痛每年造成的经济损失为360亿美元（直接医疗费用+生产力损失）。由于偏头痛，每两周就有超过13万学日缺课。然而，没有一种预防药物被fda批准用于儿童偏头痛，儿科临床实践指南是基于共识的，而不是基于证据的。中心问题是缺乏安慰剂对照临床试验和预防性药物治疗的比较有效性研究。为了解决这个问题，我们提出了“阿米替林和托吡酯预防儿童偏头痛”的试验。这个关键的儿科项目将在一个临床试验中解决三个关键问题。总的来说，结果将改变临床医生可用的知识库，并提供改变和优化实践所需的重要证据。由于阿米替林（AMI）和托吡酯（TPM）是儿科头痛专家常用的药物，但目前缺乏经验数据作为美国神经病学学会实践参数推荐的一级证据，因此前两个问题涉及两种药物相对于安慰剂的疗效、耐受性和安全性。第三个问题第一次针对儿童提出，这两种药物在疗效、耐受性和安全性方面如何比较。我们的目标是使用专门为该项目开发的决策算法确定儿童偏头痛的首选预防药物治疗。我们将进行一项三组、随机、双盲、平行组、安慰剂对照试验，测试AMI和TPM，从美国多达40个地点招募675名8至17岁的偏头痛儿童和青少年。参与者将以2:2:1的方式随机分配（AMI [N=270]; TPM [N=270]；安慰剂[N=135]），并将接受预防药物治疗或安慰剂治疗24周。主要终点是在这项为期24周的临床试验的最后4周内，偏头痛频率从基线（通过每日疼痛日记测量）减少50%。关键的次要终点将是偏头痛相关的残疾、耐受性和安全性。

DESCRIPTION (provided by applicant): Migraine affects more than 6 million children and adolescents in the United States and the majority continue to experience migraines into adulthood. The annual economic impact of migraine in the U.S. is $36 billion (direct medical costs + lost productivity). Over 130,000 school days are missed every two weeks due to migraine. Yet, no prevention medication is FDA-approved for childhood migraine and pediatric clinical practice guidelines are consensus-based, not evidence-based. The central problem is the lack of placebo-controlled clinical trials and comparative effectiveness studies of prophylactic medication therapy. To address this problem, we propose the 'Amitriptyline and Topiramate in the Prevention of Childhood Migraine' Trial. This pivotal pediatric project will address three critical questions in one clinical trial. Collectively, the results will transform the knowledge base available to clinicians and provide vital evidence needed to change and optimize practice. Because amitriptyline (AMI) and topiramate (TPM) are commonly used by pediatric headache specialists, but currently lack the empirical data to be recommended as Class I evidence in the American Academy of Neurology practice parameters, the first two questions address the efficacy, tolerability, and safety of the two medications relative to placebo. The third question asks, for the first time with children, how these two medications compare to each other in terms of efficacy, tolerability, and safety. Our goal is to determine the first choice prevention medication therapy for pediatric migraine using a decision algorithm developed specifically for this project. We will conduct a 3-arm, randomized, double-blind, parallel group, placebo-controlled trial testing AMI and TPM with 675 children and adolescents between age 8 and 17 with migraine recruited from up to 40 sites across the United States. Participants will be randomized in a 2:2:1 fashion (AMI [N=270]; TPM [N=270]; Placebo [N=135]) and will receive prevention medication therapy or placebo for 24 weeks. The primary endpoint will be a > 50% reduction in migraine frequency from baseline (measured by daily pain diary) during the final 4 weeks of this 24-week clinical trial. Key secondary endpoints will be migraine-related disability, tolerability, and safety.