Thalassemia Clinical Research Network

地中海贫血临床研究网络

• 批准号: 6965067
• 负责人: PATRICIA J GIARDINA
• 金额: $ 21.59万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6965067
• 关键词: arginine; blood disorder chemotherapy; cardiovascular disorder; chelating agents; chelation therapy; clinical research; clinical trial phase II; combination chemotherapy; combination therapy; cooperative study; deferoxamine; drug screening /evaluation; heart function; human subject; human therapy evaluation; iron disorder; longitudinal human study; medical complication; patient /disease registry; patient oriented research; pulmonary hypertension; thalassemia

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.

描述（由申请人提供）： 这是地中海贫血临床研究网络 (TCRN) 的一项为期五年的更新申请，其使命是加速地中海贫血治疗的研究，其中包括 ¿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；和 α 地中海贫血：纯合子、血红蛋白 H 病和 HbH/Constant Spring 该网络由美国的四个核心站点、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多个站点组成。根据与 NHLBI 的合作协议，将较小的区域“卫星”站点连接到核心中心。 TCRN 的主要优势包括研究人员和站点的合作能力。标准化患者评估和护理；通过观察性、介入性和辅助设计来设计、实施和进行临床试验，由于样本量的考虑，多中心网络至关重要。 TCRN 注册中心，从中确定试验受试者，该注册中心目前包括来自 22 个地点的 800 多名患者，其中包括 ¿ -重型地中海贫血（n=422），¿ -thal 中间体 (n=121)，Hb E/ ¿ thal (n=103)、输血依赖性 a-thal Major (n=9)、HbH 疾病 (n=105) 和 HbH/Constant Spring (n=44) 续签补助金的具体目标是：( I) 在地中海贫血护理的关键领域进行介入临床试验，建议开展两项试验，以检验单独去铁胺与去铁胺加用的效果。去铁酮，治疗因输血铁超载引起的心脏病。第二，精氨酸与安慰剂治疗肺动脉高压的随机试验，肺动脉高压是中间型地中海贫血和其他溶血状态的一个重要问题（II），为开发、启动和及时提供基础设施。完成地中海贫血的小型创新试验。（III）改善地中海贫血表型和临床结果的评估，以促进当前和未来的临床试验。地中海贫血纵向队列研究，以及铁相关器官损伤的详细研究，将心脏、肝脏和胰腺的铁负荷测量结果与铁相关器官功能障碍的结果相结合，并结合拟议的临床试验和能力。执行详细的基因型/表型相关性，这些改进的表型和结果测量是增强地中海贫血临床护理知识的有力工具，正如 NIH 2003 年主任路线图所设想的那样。