Thalassemia Clinical Research Network, Canada

加拿大地中海贫血临床研究网络

• 批准号: 7269941
• 负责人: NANCY F OLIVIERI
• 金额: $ 17.76万
• 依托单位: UNIVERSITY HEALTH NETWORK
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269941
• 关键词: Thalassemia; Clinical; Research; Network; Canada

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 deferiprone, 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) 的五年续展申请。 TCRN 的使命是加速地中海贫血治疗的研究。该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上血红蛋白 E/地中海贫血； α 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核心中心的几个较小的区域“卫星”站点组成。 TCRN 的主要优势包括研究人员和中心合作标准化患者评估和护理的能力；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。出于样本量的考虑，多中心网络至关重要。初始资助期的一项关键成就是建立和分析 TCRN 登记处，从中确定试验对象。该登记目前包括来自 22 个地点的 800 多名患者，包括重型 地中海贫血 (n=422)、中间型地中海贫血 (n=121)、Hb E/ 地中海贫血 (n=103)、输血依赖性重型地中海贫血 (n=9)、HbH 疾病 (n=105) 和 HbH/Constant Spring (n=44)。续签拨款的具体目标是：（一）在地中海贫血治疗的关键领域开展介入临床试验。提议进行两项试验。首先，这是一项随机对照试验，旨在检查单独的去铁胺与去铁胺加去铁酮对输血铁超负荷引起的心脏病的影响。其次，一项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) 为地中海贫血小型创新试验的开发、启动和迅速完成提供基础设施。 （三）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。这将通过两项研究来完成。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，比较了心脏、肝脏和胰腺中铁负荷的测量结果与铁相关器官功能障碍的结果。结合拟议的临床试验和执行详细基因型/表型相关性的能力，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强大工具，正如 NIH 2003 年主任路线图所设想的那样。