PILOT EXPLORATIONS OF ZINC EFFECTS IN ADHD

描述(由申请人提供)：本申请旨在开发直接从锌补充治疗注意力缺陷/多动障碍(ADHD)的试点数据，以便能够自信地计算效果大小，并提供设计锌作为ADHD治疗的最终试验所需的其他信息，无论是单独治疗还是作为刺激剂的辅助。锌对大脑功能/发育是必不可少的。它是100种代谢过程的金属酶，涉及必需脂肪酸、其代谢物、神经递质和褪黑素，褪黑素调节大脑多巴胺活动，据信ADHD缺乏褪黑素。专家怀疑，即使在美国，也普遍存在轻微(亚临床)缺锌。缺锌的症状包括注意力障碍和“紧张”。多份报告显示，ADHD患者的锌水平低于正常对照组或实验室正常水平。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)。安慰剂对苯丙胺的反应似乎与锌营养的充分性呈线性关系。两项中东试验表明，补锌有益。如果锌补充剂能够被证明是一种有效的治疗ADHD的方法，无论是单独的还是作为刺激剂的辅助，它将具有巨大的公共卫生重要性。由于缺乏从美国饮食中实际补充锌对ADHD影响的试点数据，可以自信地计算出影响大小，因此适当的临床试验一直受到阻碍。该应用程序将收集必要的试验数据，并报告计划试验所需的效果大小和其他信息。设计/假设：同一受试者中的三项紧密联系的研究(实际上是分阶段进行的)将比较每天1 SMG补锌(RDA/RDI)与安慰剂加和不加苯丙胺的效果，以确定单一治疗效果大小、辅助治疗效果大小以及对最佳苯丙胺剂量的影响。第一阶段将52名6-14岁的儿童随机服用锌或锌匹配的安慰剂，为期8周。第二阶段在两个随机组中加入固定剂量的苯丙胺(0.5 mg/kg/天)，为期2周。阶段3在3周内将安非他明滴定到最佳临床结果，保持原来的随机化。结果测量包括第一阶段和第二阶段的父母/教师评定的ADHD症状，以及第三阶段的苯丙胺最佳剂量。组织锌将通过三种最先进的分析方法来确定。

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.