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: 10254152
• 负责人: GERVASIO A LAMAS
• 金额: $ 117.18万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254152
• 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.

项目总结/摘要 评估螯合疗法2（TACT 2 M）试验中的金属的主要目的是评估 长期的基于乙二胺四乙酸二钠（EDTA）的螯合输注是否可以显著降低体内铅含量， 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 是EDTA螯合疗法引起的TACT 2 M是TACT 2的伴随研究，将被整合到 TACT 2的临床试验平台，将入组1200例年龄至少50岁的MI后糖尿病患者 年龄较大，肌酐≤ 2.0 mg/dL。TACT 2是TACT（简称TACT 1）的重复研究， 是一项2X2析因试验，将患者随机分为4组，定义为活性药物输注与安慰剂输注， 活性与安慰剂口服多种维生素和多种矿物质（OMVM）。NCCIH资助了UG 3 1年规划 TACT 2阶段。TACT 2 M的协同主要终点是：1]血铅水平从基线至 输注40年或1年，以先发生者为准，2]肌酐控制的尿镉变化（Cd mcg/ 克肌酸酐）从基线到输注40年或1年，以先发生者为准。 TACT 2 M有3个具体目的：1）比较金属内剂量（血铅和尿镉）的变化 在TACT 2受试者中，活性输注组从基线至输注40年或1年; 2]评价是否 较高的基线金属体内剂量（血铅和尿镉）和这些储存的消耗程度 确定患者更有可能从螯合治疗中获益; 3]收集标本的生物储存库，以支持 未来的机械化工作。全血和尿液样本将在-80播放C下储存在安全的生物储存库中， 确保其可用于评估未来的假设，这些假设将以试验结果为指导。 此外，TACT 2 M是评估以下探索性目标的独特机会： 单独的输注尿液测量值以及与相应的输注前测量值相比， 临床意义; B] OMVM是否与依地酸二钠介导的金属排泄相互作用;和c] 通过ICPMS分析仪在血液和尿液中测量的其他有毒和必需金属套件是否 金属实验室使用的技术，其中许多不被乙二胺四乙酸二钠螯合， 初步测试的意义。 总之，TACT 2 M将评估金属螯合是否是改善临床症状的可能机制。 接受依地酸二钠螯合治疗的MI后糖尿病患者的结局。将TACT 2 M整合到 现有的TACT 2研究是告知有MI病史患者治疗的有效方法， 糖尿病