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

评估螯合疗法 2 试验中的金属 (TACT2M)

• 批准号: 9688920
• 负责人: GERVASIO A LAMAS
• 金额: $ 100万
• 依托单位: MOUNT SINAI MEDICAL CENTER (MIAMI BEACH)
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9688920
• 关键词: Blood; Blood specimen; Cadmium; Cardiovascular Diseases; Cardiovascular system; Chelation Therapy; Clinical; Clinical Trials; Companions; Creatinine; Data; Development; Diabetes Mellitus; Dose; Elements; Enrollment; Ensure; Environment; Epidemiology; Evaluation; Event; Excretory function; Funding; Future; Grant; Half-Life; Individual; Infusion procedures; Lead; Lead levels; Measurement; Measures; Mediating; Metals; Methods; Multivitamin; Myocardial Infarction; Oral; Outcome; Participant; Patients; Pattern; Phase; Placebos; Plasma; Randomized; Recording of previous events; Role; Sampling; Secure; Solid; Specimen; Techniques; Testing; Urine; Whole Blood; Work; arm; base; biobank; blood lead; bone; cardiovascular risk factor; causal model; chelation; clinically significant; diabetic patient; exposed human population; improved; innovation; lead exposure; outcome prediction; primary endpoint; prognostic significance; soft tissue; toxic metal; treatment duration

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.

项目概要/摘要 评估螯合疗法 2 试验 (TACT2M) 中金属的主要目标是评估 长期注射基于乙二胺四乙酸二钠（EDTA）的螯合输注是否可以显着降低体内铅和 镉水平并确定这种效应是否可以解释主要心血管事件的减少 由EDTA螯合疗法引起。 TACT2M 是 TACT2 的配套研究，将被整合到 TACT2临床试验平台将招募1200名50岁以上的MI后糖尿病患者 年龄较大且肌酐为 2.0 mg/dL 或更低。 TACT2是TACT（简称TACT1）的复制研究，将 是一项 2X2 析因试验，将患者随机分为 4 组，根据活性药物输注与安慰剂输注进行定义， 活性与安慰剂口服多种维生素和多种矿物质 (OMVM)。 NCCIH 资助了 UG3 1 年规划 TACT2 阶段。 TACT2M 的共同主要终点是： 1] 血铅水平从基线到 输注 40 或 1 年，以先到者为准，以及 2] 尿镉控制肌酐的变化（Cd mcg/ 克肌酐）从基线到输注 40 或 1 年，以先到者为准。 TACT2M 有 3 个具体目标： 1] 比较金属内部剂量的变化（血铅和尿镉） 在 TACT2 参与者中，从基线到主动输注臂输注 40 或 1 年； 2]评估是否 较高的基线金属内部剂量（血铅和尿镉）以及这些储备的消耗程度 确定更有可能从螯合中获益的患者； 3]收集样本生物储存库以支持 未来的机械工作。全血和尿液样本将储存在 -80°C 的安全生物样本库中 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 提供了评估以下探索性目标的独特机会：a] 是否 单独进行输注尿液测量并与相应的输注前测量相比， 临床意义； b] OMVM是否与乙二胺四乙酸二钠介导的金属排泄相互作用；和c] ICPMS 分析是否在血液和尿液中测量了一系列其他有毒金属和必需金属 金属实验室使用的技术，其中许多不被依地酸二钠螯合，具有临床意义 在初步测试中具有重要意义。 总之，TACT2M 将评估金属螯合是否是改善临床的可能机制。 接受依地酸二钠螯合的 MI 后糖尿病患者的结果。 TACT2M 的集成 现有的 TACT2 研究是一种有效的方法，可以为有 MI 病史的患者提供治疗信息， 糖尿病。