Thalassemia Clinic Research Network

描述(由申请人提供)： 这是地中海贫血临床研究网络(TCRN)的五年续签申请。TCRN的使命是加快地中海贫血管理的研究。这项任务涵盖的综合征包括地中海贫血：纯合子或复合杂合子加血红蛋白E/地中海贫血；以及阿尔法地中海贫血：纯合子、血红蛋白H病和HBH/Constant Spring。根据与NHLBI的合作协议，该网络由四个美国核心站点、一个数据协调中心、美国、加拿大和英国的几个大型附属临床站点以及几个与核心中心相连的较小的地区性“卫星”站点组成。TCRN的主要优势包括研究人员和现场合作标准化患者评估和护理的能力；通过观察性、干预性和辅助设计设计、实施和进行临床试验。由于样本大小的考虑，多中心网络一直至关重要。最初赠款期间的一项关键成就是建立和分析了技术合作与合作网络登记处，从中确定了试验对象。登记的患者包括22个地点的800多名患者，包括重型地中海贫血422例，中间地中海贫血121例，Hb E/Thal 103例，输血依赖型α-Thal 9例，HBH病L 05例，HBH/Constant Spring 44例。续期赠款的具体目的是：(I)在地中海贫血护理的关键领域进行介入性临床试验。建议进行两项试验。首先，一项随机对照试验，检验去铁胺单独治疗与去铁胺加去铁酮治疗输血铁负荷过多引起的心脏病的效果。第二，精氨酸与安慰剂治疗肺动脉高压的随机试验，这是中间地中海贫血和其他溶血状态的一个重要问题。(2)为地中海贫血小规模创新试验的开发、启动和迅速完成提供基础设施。(ILL)改进对地中海贫血的表型和临床结果的评估，以促进当前和未来的临床试验。这将通过两项研究来实现。地中海贫血纵向队列研究，以及对铁相关器官损伤的详细研究，将心脏、肝脏和胰腺的铁负荷指标与铁相关器官功能障碍的结果进行比较。结合拟议的临床试验和执行详细的基因型/表型相关性的能力，这些改进的表型和结果测量方法是增强地中海贫血临床护理知识的有力工具，正如美国国立卫生研究院2003年主任路线图所设想的那样。

DESCRIPTION (provided by applicant): This is a five-year renewal application for the Thalassemia Clinical Research Network (TCRN). TCRN's mission is to accelerate research in the management of thalassemia. Syndromes encompassed by this mission include the ¿ thalassemias: homozygous or compound heterozygous plus Hemoglobin E/¿ thalassemia; and the alpha thalassemias: homozygous, hemoglobin H disease, and HbH/Constant Spring. The network is composed of four core U.S. sites, a data coordinating center, several large affiliated clinical sites in the U.S., Canada, and England, and several smaller regional "satellite" sites to the core centers, in a cooperative agreement with NHLBI. Key strengths of the TCRN include a demonstrated ability of the investigators and sites cooperatively to standardize patient assessment and care; to design, implement and conduct clinical trials with observational, interventional, and ancillary designs. The multicenter network has been crucial due to sample size considerations. A pivotal accomplishment of the initial grant period is the establishment and analysis of the TCRN Registry, from which subjects for trials are identified. The registry now includes over 800 patients from 22 sites, including ¿-thalassemia major (n=422), ¿ -thal intermedia (n=121), Hb E/ ¿ thal (n=103), transfusion-dependent a-thal major (n=9), HbH disease (n=l 05), and HbH/Constant Spring (n=44). The Specific Aims of the renewal grant are: (I) To perform interventional clinical trials in key areas of thalassemia care. Two trials are proposed. First, a randomized, controlled trial to examine the effect of deferoxamine alone v. deferoxamine plus deferriprone, on cardiac disease due to transfusional iron overload. Second, a randomized trial of arginine v. placebo for pulmonary hypertension, an important problem in thalassemia intermedia and other hemolytic states. (II) To provide an infrastructure for development, launch, and prompt completion of small, innovative trials in thalassemia. (Ill) To improve assessment of phenotype and clinical outcomes in thalassemia, in order to facilitate current and future clinical trials. This will be accomplished by two studies. The Thalassemia Longitudinal Cohort study, as well as a detailed study of iron-related organ damage, comparing measures of iron burden in the heart, liver and pancreas, to outcomes of iron-related organ dysfunction. Combined with the proposed clinical trials and the ability to perform detailed genotype/phenotype correlations, these improved phenotype and outcome measures are powerful tools to enhance knowledge about thalassemia clinical care, as envisioned by the NIH's 2003 Director's Roadmap.