PILOT EXPLORATIONS OF ZINC EFFECTS IN ADHD

描述（由申请人提供）：本申请旨在直接从注意力缺陷/多动障碍（ADHD）的锌补充中开发试验数据，以允许可靠地计算效应量，并提供设计锌单独或作为兴奋剂辅助治疗ADHD的确定性试验所需的其他信息。锌对大脑功能/发育至关重要。它是100种代谢过程的金属酶，涉及必需脂肪酸，其代谢物，神经递质和褪黑激素，褪黑激素调节大脑多巴胺活性，被认为是ADHD的缺陷。专家怀疑即使在美国也存在广泛的边缘（亚临床）缺锌。缺锌的症状包括注意力障碍和“神经过敏”。多份报告显示，ADHD患者的锌水平低于正常对照组或实验室标准。父母/教师评定的注意力不集中症状与血清锌呈负相关（r= 0.45）。安慰剂对照组对安非他明的反应似乎与锌营养充足呈线性关系。两项中东试验表明锌补充剂有益。如果锌补充剂可以单独或作为兴奋剂的辅助治疗ADHD，它将具有巨大的公共卫生重要性。由于缺乏美国饮食中实际补锌对ADHD影响的试点数据，一项适当的临床试验一直受到阻碍，从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，并报告计划试验所需的效应量和其他信息。设计/假设：在相同受试者中进行的三项紧密联系的研究（实际上是阶段性研究）将比较15 mg/天锌补充剂（RDA/RDI）与安慰剂（伴或不伴苯丙胺），以确定单药治疗效应量、连续治疗效应量和对最佳苯丙胺剂量的影响。第一阶段将52名6-14岁的儿童随机分为锌组或锌匹配安慰剂组，为期8周。第2阶段在两个随机化组中添加固定剂量的安非他明（0.5 mg/kg/天），持续2周。第3阶段在3周内将安非他明滴定至最佳临床结果，保持原始随机化。结果的措施包括家长/教师评定的ADHD症状的阶段1和2，和安非他明的最佳剂量的阶段3。组织锌将通过3种最先进的测定法进行测定。

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.