New England, New York and Quebec Regional Clinical Center

新英格兰、纽约和魁北克地区临床中心

• 批准号: 7881714
• 负责人: MARTIN M LEWINTER
• 金额: $ 30.85万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7881714
• 关键词: Advanced Glycosylation End Products; Agonist; Anti-Inflammatory Agents; Anti-inflammatory; Biological Markers; Biopsy; Blood; Blood Vessels; Cardiac Surgery procedures; Clinical; Clinical Research; Clinical Trials; Collagen; Commit; Defect; Diabetes Mellitus; Disease; Elements; Enrollment; Functional disorder; Goals; Healthcare; Heart; Heart failure; Human Resources; Hypertension; In Vitro; Inflammation; Inflammatory; Institution; Insulin Resistance; Massachusetts; Medical center; Metabolic; Methods; Myocardial; Myocardium; New England; New York; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Oxidative Stress; Participant; Patients; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Population; Private Practice; Property; Quebec; Regimen; Risk; Risk Factors; Skin; Staging; Universities; Vermont; abstracting; adiponectin; crosslink; diabetic cardiomyopathy; experience; follow-up; hospital bed; improved; primary outcome; randomized placebo controlled trial; rural area; secondary outcome; tertiary care

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)

描述（由申请人提供）： 这是一份指定为心力衰竭 (HF) 临床研究网络区域临床中心 (RCC) 的申请。参与者来自新英格兰北部、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中心（赞助机构）、奥尔巴尼/圣路易斯大学。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。拟议的 RCC 拥有超过 6,000,000 名三级医疗服务人口和 3,500 多个病床。 2004年，新发现的心力衰竭患者超过2300名，每周随访的心力衰竭患者超过180名。 RCC 还包括佛蒙特州和纽约州私人诊所的心脏病专家，他们致力于招募来自农村地区、很少参加临床试验的患者。关键人员在多中心试验的规划和管理方面拥有丰富的经验，每个机构的当地 PI 都是经验丰富的参与者。计划开展各种合作活动以维持充满活力的区域网络。 RCC 的两个拟议项目共享 a.共同主题，2 型糖尿病 (DM) 作为心力衰竭的危险因素和机制。项目 #1 是一项安慰剂对照、随机试验，研究噻唑烷二酮用于治疗舒张功能障碍 (DD)，这是一种常见且常见的疾病。 糖尿病心肌病的早期表现。次要结果是收缩功能障碍以及促炎和促纤维化生物标志物血液水平的变化。项目#2 采用我们开发的方法来研究心脏手术期间获得的“带皮”心肌条以及来自末期移植心脏的心肌条。通过使用手术活检，我们可以检查可导致心力衰竭的非终末期疾病状态，并描述疾病特定的病理生理学和药物作用要素。我们将使用这些方法来确定药物 Alagebrium（一种晚期糖基化终产物 (AGE) 相关胶原交联的破坏剂）对 DM、高血压 (HTN) 和糖尿病患者被动僵硬的体外、疾病特异性影响。 DM+HTN。 AGEs被认为会导致这些患者的心肌和血管僵硬度增加。结果将与术前 DD 和免疫电子显微镜对 AGE 的评估相关联。我们针对 RCC 提出的研究有可能降低糖尿病患者发生心力衰竭的风险。活检研究将增进对病理生理学以及药物作用和机制的了解。 （摘要完）