METHYLPHENIDATE EFFICACY AND SAFETY IN ADHD PRESCHOOLERS

描述（改编自申请人的摘要）：这种六位点平行RO 1 申请要求资助一项为期三年的有效性和安全性研究， 哌甲酯（MPH）在学龄前儿童注意力缺陷/ 多动症（ADHD）。虽然MPH在所有年龄组的使用是 其包装说明书禁止学龄前儿童使用。 以前的MPH学前治疗研究对象很少，他们的结果 不能组合以产生所需的安全信息。拟定的研究将 通过对44名ADHD患者进行6个地点的对照试验来解决这些问题。 每个站点有264名儿童，共计264名儿童。它将设在纽约 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）、加州大学洛杉矶分校 （UCLA）和位于欧文的加州大学（UCI）。每个研究中心的受试者 （N=44）将包括：第1组，ADHD学龄前儿童（n=33），年龄3-5岁，6 个月;第2组（n=11），ADHD对照组，年龄6-8岁。经过评估， 所有的孩子都将进入一个四部分的研究。I期为3周开放标签 MPH的安全性滴定试验，2.5 - 10 mg/剂，每日3次（t.i.d.）。 那些没有损害副作用的人将进入第二阶段， 随机分配的双盲、安慰剂对照、滴定试验 （每周）安慰剂或MPH的4个剂量之一（2.5，5，7.5和10 mg/剂量）并在实验室（模拟）教室中监测一次。第三阶段将 是一个开放标签，为期一年的扩展，第四阶段将是一个双盲， 安慰剂停药试验。目的I是确定 患有ADHD的学龄前儿童的MPH。目的2是检验组间差异 1和2对MPH的剂量反应。目的3是检查两个假定的风险位点， 多巴胺D4受体基因（DRD 4）或多巴胺转运蛋白基因（DATI）， 在一项以家庭为基础的亲子关联研究中， 等位基因传递，以及对MPH的剂量反应是否与通用 这两个基因座的变异性

DESCRIPTION (Adapted from Applicant's Abstract): This six-site parallel RO1 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.