Metals in the Trial to Assess Chelation Therapy 2 (TACT2M)

项目摘要/摘要 金属试验评估螯合疗法2(TACT2M)的主要目标是评估 以乙二胺四乙酸二钠(EDTA)为基础的长期输液是否可以显著降低体内铅和 并确定这一效应是否可以解释重大心血管事件的减少 由EDTA螯合疗法引起。TACT2M是TACT2的配套研究，将被整合到 TACT2临床试验平台，将纳入1200名50岁以上的心肌梗塞后糖尿病患者 年龄较大，肌酐为2.0 mg/dL或更低。TACT2是对TACT的复制研究(简称TACT1)，它将 为2X2析因试验，将患者随机分成4组，由活性输液与安慰剂输注和 活性与安慰剂口服复合维生素和多种矿物质(OMVM)。NCCIH为UG3一年规划提供资金 TACT2阶段。TACT2M的共同主要终点是：1)血铅水平从基线到 输液40年或1年，以先输者为准；2)尿镉控制肌酐(Cd MCG/)的变化 从基线到输液40年或1年，以最先的为准。 TACT2M有3个具体目标：1)比较金属内剂量(血铅和尿镉)的变化 在TACT2参与者中，从基线到主动输液组40年或1年；2]评估 较高的基线金属内剂量(血铅和尿镉)以及这些储存的耗尽程度 确定更有可能从螯合中受益的患者；3)收集样本的生物信息库以支持 未来的机械化工作。全血和尿样将储存在-80°C的安全生物储存库中，以 确保它们可用于评估将以试验结果为指导的未来假设。 此外，TACT2M是评估以下探索性目标的独特机会：a]是否后 单独和与相应的输液前测量相比，输液尿液测量具有 临床意义；b]OMVM是否与依地特二钠介导的金属排泄相互作用；以及c] ICPMS分析在血液和尿液中检测到的额外有毒和必需金属 金属实验室使用的技术，其中许多不被依地他二钠螯合，具有临床应用价值 在初步测试中的意义。 综上所述，TACT2M将评估金属螯合是否为改善临床的一种可能机制 接受依地特二钠螯合治疗的心肌梗死后糖尿病患者的预后。将TACT2M集成到 现有的TACT2研究是一种有效的方法，可以告知有MI和 糖尿病。

Project Summary/Abstract The main objectives of the Metals in the Trial to Assess Chelation Therapy 2 (TACT2M) are to evaluate whether long-term edetate disodium (EDTA)-based chelation infusions can significantly reduce body lead and cadmium levels and to determine whether this effect explains the reduction in major cardiovascular events caused by EDTA chelation therapy. TACT2M is a companion study to TACT2 and will be integrated into the clinical trial platform of TACT2, which will enroll 1200 post-MI patients with diabetes who are at least 50 years old and have a creatinine of 2.0 mg/dL or less. TACT2, a replication study of TACT (referred to as TACT1), will be a 2X2 factorial trial, randomizing patients to 4 groups, defined by both active vs placebo infusions and active vs placebo oral multivitamins and multiminerals (OMVM). NCCIH has funded the UG3 1-year Planning Phase of TACT2. The co-primary endpoints of TACT2M are: 1] the change in blood lead level from baseline to infusion 40 or 1 year, whichever is first, and 2] the change in urine cadmium controlled for creatinine (Cd mcg/ gram creatinine) from baseline to infusion 40 or 1 year, whichever is first. TACT2M has 3 Specific Aims: 1] Compare the change in metal internal dose (blood lead and urine cadmium) in TACT2 participants, from baseline to infusion 40 or 1 year in the active infusion arm; 2] Evaluate whether higher baseline metal internal dose (blood lead and urine cadmium) and the extent of depletion of those stores identifies patients more likely to show benefit from chelation; 3] Collect a biorepository of specimens to support future mechanistic work. Samples of whole blood and urine will be stored at -80ºC in a secured biorepository to ensure their availability for the evaluation of future hypotheses that will be guided by the results of the trial. Moreover, TACT2M represents a unique opportunity to assess the following Exploratory Aims: a] whether post- infusion urine measurements, alone and in comparison to the corresponding pre-infusion measurements, have clinical significance; b] whether OMVM interact with edetate disodium-mediated metal excretion; and c] whether the suite of additional toxic and essential metals measured in blood and urine by the ICPMS analytic technique used by the metals lab, many of which are not chelated by edetate disodium, have clinical significance in preliminary testing. In summary, TACT2M will assess whether metal chelation is a possible mechanism for improved clinical outcomes in post-MI diabetic patients receiving edetate disodium chelation. The integration of TACT2M into the existing TACT2 study is an efficient method to inform the treatment of patients with a history of MI and diabetes.