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: 8588997
• 负责人: GORDON S HUGGINS
• 金额: $ 33.03万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588997
• 关键词: Achievement; Activities of Daily Living; Appearance; Biological Markers; Cardiac; Cardiology; Clinical; Clinical Trials; Collaborations; Communication; Coronary Artery Bypass; Double-Blind Method; EFRAC; Echocardiography; Enrollment; Evidence based treatment; Exercise; Fostering; Foundations; Frequencies; Functional disorder; Funding; Healthcare; Heart Transplantation; Heart failure; Hypertrophy; In Vitro; Institutes; Instruction; Ischemia; Joints; Laboratories; Leadership; Left; Left Ventricular Hypertrophy; Left Ventricular Mass; Left Ventricular Remodeling; Magnetic Resonance Imaging; Measures; Medical center; Modality; Myocardial; National Heart, Lung, and Blood Institute; New England; New York; Patient Care; Patients; Performance; Pharmaceutical Preparations; Phase II Clinical Trials; Placebo Control; Placebos; Productivity; Publishing; Pulmonary artery structure; Quality of life; Quebec; Questionnaires; Radioisotopes; Randomized; Renal function; Research; Research Personnel; Resource Development; Resources; Serum; Site; Staging; Structure; Symptoms; Systolic Pressure; Testing; Training; Training Programs; Translational Research; Transplantation; Universities; Ventricular; Ventricular Remodeling; Vermont; evidence base; improved; indexing; novel; programs; randomized trial; ranolazine; secondary outcome

DESCRIPTION (provided by applicant): This application is a renewal of the New England, New York and Quebec Regional Clinical Center of the NHLBI Heart Failure Research Network, under the direction of Dr. Martin LeWinter of the University of Vermont and Fletcher Allen Health Care (UVM/FAHC). With this application we propose a new leadership structure, a multiple PI/PD partnership with Tufts Medical Center (Tufts MC) under the direction of Dr. Marvin Konstam, and a major expansion of the RCC. We believe that this expansion will markedly enhance both our scientific contribution to the Network and our enrollment capabilities. As our clinical trial, we propose to study the effects of ranolazine in patients with heart failure with normal ejection fraction (HFNEF). About 50% of HF patients have a normal EF. There are currently no evidence-based treatments for HFNEF. We have published in vitro studies using excitable left ventricular (LV) myocardial strips obtained from patients undergoing coronary bypass grafting which show that the presence of concentric LV hypertrophy (LVH), which is common in patients with HFNEF, is associated with the appearance of increasing diastolic tension at abnormally low stimulation frequencies. We have also shown that the anti-anginal drug ranolazine, which inhibits the late sarcolemmal Na current, normalizes this rate-dependent diastolic dysfunction. Accordingly, we propose a 24 week randomized trial of ranolazine versus placebo in patients with HFNEF and LVH to test the hypothesis that ranolazine improves exercise performance, assessed as peak V02 during either treadmill or cycle exercise. Secondary outcome variables include results of a symptom questionnaire, submaximal exercise performance, and changes in LV mass, diastolic function, and serum biomarkers of neurohumoral activation. A positive result of this trial would lay the foundation for a larger, mor definitive trial of ranolazine in treating the very difficult problem of HFNEF. RELEVANCE (See instructions): HF has become a problem of major proportions over the last two decades. Important strides have been made in improving functional capacity and survival in HF with reduced ejection fraction. However, progress in the approximately 50% of patients with normal ejection fraction has been disappointing. The proposed trial, along with expansion of our RCC, has the potential to positively impact this major clinical problem.

描述（由申请人提供）：在NHLBI心力衰竭研究网络的新英格兰，纽约和魁北克区域临床中心的续签下，佛蒙特大学和弗莱彻·艾伦医疗保健（UVM/FAHC）的指导下。通过此应用，我们提出了一种新的领导结构，在Marvin Konstam博士的指导下与Tufts医疗中心（Tufts MC）建立了多个PI/PD合作伙伴关系，以及RCC的重大扩展。我们认为，这种扩展将显着增强我们对网络的科学贡献和入学能力。作为我们的临床试验，我们建议研究雷诺嗪对正常射血分数（HFNEF）心力衰竭患者的影响。大约50％的HF患者具有正常的EF。目前尚无针对HFNEF的循证治疗方法。我们已经使用可激发的左心室（LV）心肌条发表了从接受冠状动脉搭桥术的患者获得的令人兴奋的左心室（LV）心肌条，这些条形在HFNEF患者中常见的同心LV肥大（LVH）的存在与在异常低刺激频率下增加舒张性舒张性的外观有关。我们还表明，抑制晚期肌膜NA电流的抗血管中性药物雷诺嗪将这种依赖性舒张功能障碍归一化。因此，我们在HFNEF和LVH患者中提出了24周的Ranolazine与安慰剂的随机试验，以测试雷诺嗪在跑步机或周期运动中评估为峰值V02的假设。次要结果变量包括症状问卷的结果，次最大运动表现以及LV质量，舒张功能和神经肿瘤激活的血清生物标志物的变化。这项试验的积极结果将为雷诺嗪的更大，确定性试验奠定基础，以处理非常困难的HFNEF问题。 相关性（请参阅说明）：在过去的二十年中，HF已成为主要比例的问题。在提高HF的功能能力和射血分数下降方面，已经取得了重要的进步。但是，大约50％的正常射血分数患者的进展令人失望。拟议的试验以及我们的RCC的扩展有可能对这一主要临床问题产生积极影响。