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/多动症（ADHD）补充锌中开发试点数据，以便能够自信地计算效果大小，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作为兴奋剂的辅助疗法。锌对于大脑功能/发育至关重要。它是一种金属酶，负责 100 种代谢过程，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，据信多动症患者缺乏这种活性。专家怀疑，即使在美国，也存在广泛的边缘（亚临床）锌缺乏症。缺锌的症状包括注意力障碍和“紧张不安”。多项报告显示，多动症患者的锌水平低于正常对照或实验室标准。家长/老师评价的注意力不集中症状与血清锌呈负相关（r=.45）。安慰剂对照的安非他明反应似乎与锌营养充足程度呈线性关系。两项中东试验表明，锌有益于补充锌。如果锌补充剂能够有效治疗 ADHD，无论是单独使用还是作为兴奋剂的辅助疗法，它都将具有巨大的公共健康重要性，因为缺乏美国饮食中锌补充剂对 ADHD 影响的试点数据，因此可以自信地计算出效果大小。 设计/假设：三项紧密相关的研究。相同受试者中的 1 Smg/天锌补充剂 (RDA/RDI) 与安慰剂联合或不联合安非他明进行比较，以确定单一疗法效果大小、辅助治疗效果大小以及对最佳安非他明剂量的影响，第 1 期将 52 名 6-14 岁儿童随机服用锌或锌匹配安慰剂，为期 8 周。第 3 阶段在 3 周内将安非他明调整至最佳临床结果，维持最初的随机化结果，包括第 1 和第 2 阶段家长/教师评定的 ADHD 症状，以及第 3 阶段的安非他明最佳剂量。组织锌将通过 3 项最先进的检测来确定。

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.