METHYLPHENIDATE EFFICACY AND SAFETY IN ADHD PRESCHOOLERS

描述(改编自申请者摘要)：此六站点并行R01 申请申请资助一项为期三年的有效性和安全性研究 注意缺陷学龄前儿童对哌醋甲酯(MPH)的影响 多动症(ADHD)。尽管MPH在所有年龄段的使用是 越来越多地，它的包装插页禁止在学龄前儿童中使用。 以前的MPH学龄前治疗研究对象很少，他们的结果是 不能组合在一起以产生所需的安全信息。拟议的研究将 通过对44名ADHD患者进行六个地点的对照试验来解决这些问题 每个站点的儿童，或总计264名儿童。它的总部将设在纽约 州立精神病学研究所(NYSPI)，杜克大学，约翰霍普金斯大学 (JHU)、纽约大学(NYU)、洛杉矶加州大学 (加州大学洛杉矶分校)和加州大学欧文分校(UCI)。每个站点的主题 (n=44)将包括：第1组，ADHD学龄前儿童(n=33)，3-5岁，6岁 2组(n=11)为ADHD对照组，年龄6~8岁。经过评估， 所有的孩子都将参加一个由四部分组成的研究。L阶段将为期3周，开放标签 MPH的安全滴定试验，2.5-10毫克/剂量，每日3次(Tid)。 那些没有减弱副作用的患者将进入第二阶段，为期五周 随机分配的双盲安慰剂对照滴定试验 (每周)服用安慰剂，或服用4种mph中的一种(2.5、5、7.5和10 毫克/剂量)，并在实验室(模拟)教室监测一次。第三阶段将 作为开放标签，延期一年，第四阶段将是双盲， 安慰剂停药试验。目的一是确定安慰剂的安全性和有效性 患有ADHD的学龄前儿童的公共卫生指数。目标2是测试不同组之间的差异 1和2对公共卫生的剂量反应。目标3是检查是否有两个假定的风险基因， 多巴胺D4受体基因(DRD4)或多巴胺转运蛋白基因(DATI)， 在一项基于家庭的亲子关联研究中发现与ADHD有关 等位基因传递，以及对mph的剂量反应是否与普通相关 这两个基因座的变异性。

DESCRIPTION (Adapted from Applicant's Abstract): This six-site parallel R01 application requests funding for a three year study of the efficacy and safety of methylphenidate (MPH) in preschool children with Attention-Deficit/ Hyperactivity Disorder (ADHD). Although MPH's use in all age groups is increasing, its package insert prohibits its use in preschool children. Previous MPH preschool treatment studies have few subjects, and their results cannot be combined to yield needed safety information. The proposed study will address these concerns by mounting a six-site, controlled trial of 44 ADHD children per site, or 264 children total. It will be based at the New York State Psychiatric Institute (NYSPI), Duke University, Johns Hopkins University (JHU), New York University (NYU), University of California at Los Angeles (UCLA), and University of California at Irvine (UCI). Each site's subjects (N=44) will include: Group 1, ADHD preschoolers (n=33), ages 3-5 years, 6 months; and Group 2 (n=11), a contrast ADHD group, ages 6-8. After assessment, all children will enter a four-part study. Phase l will be a 3 week, open-label safety titration trial of MPH, 2.5 - 10 mg/dose, given 3 times daily (t.i.d.). Those without impairing side effects will enter Phase 2, a five week double-blind, placebo controlled, titration trial, with random assignments (weekly) to either placebo or to one of 4 doses of MPH (2.5, 5, 7.5, and 10 mg/dose) and monitored once in a laboratory (analog) classroom. Phase III will be an open-label, one-year extension, and Phase IV will be a double-blind, placebo discontinuation trial. Aim I is to determine the safety and efficacy of MPH in preschoolers with ADHD. Aim 2 is to test for differences between Groups 1 and 2 in dose-response to MPH. Aim 3 is to examine if two putative risk loci, the dopamine D4 receptor gene (DRD4) or the dopamine transporter gene (DATI), are associated with ADHD in a family-based association study of parent to child allele transmission, and whether dose response to MPH is related to generic variability at these two loci.