New England, New York and Quebec Regional Clinical Center

描述(由申请人提供)： 这是一份被指定为心力衰竭(HF)临床研究网络地区临床中心(RCC)的申请。参与者是新英格兰北部、纽约和魁北克的不同机构，包括佛蒙特大学/弗莱彻·艾伦医疗保健(赞助机构)、奥尔巴尼/圣彼得医疗中心、天主教医疗中心、达特茅斯-希区柯克医疗中心、麦吉尔医疗中心和大学。马萨诸塞州医疗中心的。拟建的三级护理中心有超过600万人口和超过3500张医院病床。2004年，有超过2300名新的心力衰竭患者就诊，每周有超过180名心力衰竭患者接受随访。RCC还包括佛蒙特州和纽约私人执业的心脏病专家，他们致力于招募来自农村地区的患者，这些患者很少参加临床试验。关键人员在多中心试验的规划和管理方面有丰富的经验，每个机构的地方PI都是经验丰富的参与者。计划开展各种协作活动，以维持一个充满活力的区域网络。RCC的两个拟议项目都有一个共同的主题，即2型糖尿病(DM)是心力衰竭的危险因素和机制。项目1是一项安慰剂对照的随机试验，使用噻唑烷二酮治疗舒张期功能障碍(DD)，这是一种常见的 糖尿病心肌病的早期表现。次要结果是收缩功能障碍和血液促炎和促纤维化生物标志物水平的变化。项目2使用我们开发的方法来研究在心脏手术期间以及从终末期移植心脏获得的“剥皮”心肌条。通过手术活检，我们可以检查可能导致心力衰竭的非终末期疾病状态，并描述疾病特有的病理生理学因素和药物效应。我们将使用这些方法来确定药物Alagebrium对糖尿病、高血压(HTN)和DM+HTN患者被动僵硬的体外疾病特异性影响。Alagebrium是晚期糖基化终产物(AGE)相关胶原交联物的断裂剂。AGE被认为是导致这些患者心肌和血管僵硬增加的原因。结果将与术前DD和免疫电子显微镜评估年龄相关联。我们为我们的肾癌建议的研究有可能降低糖尿病患者发生心力衰竭的风险。活检研究将提高对病理生理学以及药物作用和机制的了解。(摘要结束)

DESCRIPTION (provided by applicant): This is an application for designation as a Regional Clinical Center (RCC) of the Heart Failure (HF) Clinical Research Network. The participants are a diverse group of institutions in Northern New England, New York and Quebec, including the University of Vermont/Fletcher Allen Health Care (the sponsoring institution), Albany/St. Peter's Medical Centers, Catholic Medical Center, Dartmouth-Hitchcock Medical Center, McGill Medical Center and Univ. of Massachusetts Medical Center. The proposed RCC has a tertiary care catchment population over 6,000,000 and over 3,500 hospital beds. In 2004, over 2300 new patients with HF were seen, and over 180 follow-up patients with HF were seen weekly. The RCC also includes cardiologists in private practice in Vermont and New York who are committed to enrolling patients from rural areas who rarely participate in clinical trials. Key personnel have extensive experience in planning and management of multi-center trials and local PIs at each institution are experienced participants. Various collaborative activities are planned to maintain a vibrant regional network. The two proposed projects for the RCC share a. common theme, type 2 diabetes mellitus (DM) as a risk factor for and mechanism of HF. Project #1 is a placebo-controlled, randomized trial of a thiazalodinedione to treat diastolic dysfunction (DD), a common and early manifestation of diabetic cardiomyopathy. Secondary outcomes are systolic dysfunction and changes in blood levels of pro-inflammatory and pro-fibrotic biomarkers. Project #2 employs methods we have developed to study "skinned" strips of myocardium obtained during cardiac surgery as well as from endstage, explanted hearts. By using surgical biopsies, we can examine non-end stage disease states that can cause HF and delineate disease-specific elements of pathophysiology and drug effects. We will use these methods to determine the in vitro, disease-specific effects of the drug Alagebrium, a breaker of advanced glycation end-product (AGE) associated collagen cross-links, on passive stiffness in patients with DM, hypertension (HTN) and DM + HTN. AGEs are thought to cause increased myocardial and vascular stiffness in these patients. Results will be correlated with pre-operative DD and assessment of AGEs by immuno electronmicroscopy. The studies we propose for our RCC have potential to reduce the risk of HF in patients with DM. Biopsy studies will improve understanding of pathophysiology and drug effects and mechanisms. (End of Abstract)