PILOT EXPLORATIONS OF ZINC EFFECTS IN ADHD

描述（由申请人提供）：本申请旨在直接从锌补充剂治疗注意力缺陷/多动障碍（ADHD）中开发试点数据，以便对效果大小进行自信的计算，并提供设计锌治疗ADHD的明确试验所需的其他信息，无论是单独使用还是辅助使用兴奋剂。锌对大脑功能/发育至关重要。它是一种金属酶，参与100种代谢过程，包括必需脂肪酸、它们的代谢物、神经递质和褪黑素，褪黑素调节大脑多巴胺活动，被认为是多动症患者缺乏的。专家怀疑即使在美国也存在广泛的边缘性（亚临床）锌缺乏症。锌缺乏症的症状包括注意力障碍和“神经紧张”。多份报告显示，多动症患者的锌含量低于正常对照或实验室标准。家长/老师评定的注意力不集中症状与血清锌呈负相关（r= 0.45）。对安非他明的安慰剂对照反应与锌营养充足呈线性关系。两项中东试验表明补充锌有益。如果锌补充剂能够被证明是治疗多动症的有效方法，无论是单独使用还是作为兴奋剂的辅助，它都将具有巨大的公共卫生重要性。由于缺乏美国人饮食中实际补充锌对ADHD的影响的试验数据，一项适当的临床试验受到了阻碍，从这些数据中可以自信地计算出效果大小。该应用程序将收集必要的试验数据，并报告效果大小和计划试验所需的其他信息。设计/假设：三个紧密相关的研究（实际上是阶段）将在同一受试者中比较1毫克/天补锌（RDA/RDI）与安慰剂（伴用安非他明和不伴用安非他明），以确定单药治疗效果大小、辅助治疗效果大小和对最佳安非他明剂量的影响。第一阶段随机选取52名6-14岁的儿童，给予锌或锌匹配的安慰剂8周。第二阶段在两个随机组中添加固定剂量的安非他明（0.5 mg/kg/天），持续2周。在3周的时间内，维持最初的随机化，将安非他明滴定至最佳临床结果。结果测量包括第一阶段和第二阶段父母/老师评定的ADHD症状，以及第三阶段安非他明的最佳剂量。组织锌将通过三个最先进的分析来确定。

DESCRIPTION (provided by applicant): This application aims to develop pilot data directly from zinc supplementation in attention-deficit/hyperactivity disorder (ADHD), to allow confident calculation of effect sizes and provide other information needed to design a definitive trial of zinc as treatment of ADHD, either alone or as adjunct to stimulant. Zinc is essential to brain function/development. It is a metalloenzyme for 100 metabolic processes involving essential fatty acids, their metabolites, neurotransmitters, and melatonin, which regulates brain dopamine activity, believed deficient in ADHD. Experts suspect widespread marginal (subclinical) zinc deficiency even in the U.S. Symptoms of Zn deficiency include attentional impairment and 'jitters". Multiple reports show lower zinc levels in ADHD than in normal controls or lab norms. Parent/teacher-rated inattention symptoms correlate inversely (r=.45) with serum zinc. Placebo-controlled response to amphetamine appears linear with adequacy of zinc nutrition. Two midEastern trials suggest benefit from zinc supplementation. If zinc supplementation could be shown an effective treatment for ADHD, either alone or as adjunct to stimulant, it would have tremendous public health importance. A proper clinical trial has been stymied by lack of pilot data for effects on ADHD from actual zinc supplementation of an American diet, from which effect sizes can be calculated confidently. This application will gather the necessary pilot data and report the effect sizes and other information needed to plan a trial. Design/Hypotheses: Three tightly-linked studies (actually phases) in the same subjects will compare 1 Smg/day zinc supplementation (RDA/RDI) to placebo with and without concomitant amphetamine to determine monotherapy effect size, adjunctive therapy effect size, and effect on optimal amphetamine dose. Phase 1 randomizes 52 children age 6-14 to either zinc or Zn-matched placebo for 8 weeks. Phase 2 adds fixed-dose amphetamine (0.5 mg/kg/day) to both randomized groups for 2 weeks. Phase 3 titrates the amphetamine to optimal clinical result over a 3 week period, maintaining the original randomization. Outcome measures include parent/teacher-rated ADHD symptoms for phases 1&2, and amphetamine optimal dose for phase 3. Tissue zinc will be determined by 3 state-of-the-art assays.