The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure

IL-1 阻断对近期失代偿性收缩性心力衰竭患者运动能力的影响

基本信息

批准号：
10222756
负责人：
Antonio Abbate
金额：
$ 57.27万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222756
关键词：
Activities of Daily Living Acute Admission activity Aerobic Exercise Aldosterone Angiotensin II Animal Model Anti-Inflammatory Agents Blood Vessels Breathing Cardiac Cardiopulmonary Clinical Clinical Trials Complex Coupling Data Diagnosis Disease Disease Marker Disease Progression Doctor of Pharmacy Doctor of Philosophy Doppler Echocardiography Double-Blind Method EFRAC Event Exertion Fatigue Fingers Functional disorder Heart failure Hospitalization Hospitals Human Impairment Incidence Inflammation Inflammatory Interleukin-1 Interruption Knowledge Life Expectancy Measures Mediator of activation protein Morbidity - disease rate Myocardial Norepinephrine Outcome Oxygen Oxygen Consumption Pathway interactions Patients Performance Pharmacology Phase Phase II Clinical Trials Phase III Clinical Trials Pilot Projects Placebos Play Plethysmography Prevalence Prognosis Quality of life Randomized Recombinants Relaxation Reporting Research Personnel Risk Factors Role Site Stroke Symptoms Syndrome Systolic heart failure Testing Work adjudication adverse outcome anakinra cardiac depression cost cytokine design disease natural history exercise capacity follow-up functional disability heart function hemodynamics hospital readmission human old age (65+)improved mortality novel novel therapeutic intervention older patient pressure primary endpoint readmission rates reduce symptoms secondary endpoint systemic inflammatory response therapy design treatment optimization treatment strategy uptake

项目摘要

Project Summary This application is for a Single-Site Investigator-Initiated Clinical Trial (R61/R33) entitled “Effects of Interleukin-1 blockade on exercise capacity in patients with recently decompensated systolic heart failure” submitted by Antonio Abbate MD, PhD and Benjamin Van Tassell, PharmD. Heart failure (HF) is a complex clinical syndrome characterized by fatigue and labored breathing upon exertion. Although current treatment options have extended life expectancy, prognosis for HF remains poor and HF is the leading cause of admission among elderly patients in the US. There is an urgent need to develop novel treatments to alleviate symptoms, slow disease progression, and reduce HF hospitalization. A significant correlation exists between declining cardiac function and increasing levels of inflammatory cytokines in HF patients. Among these cytokines, Interleukin-1 (IL-1) is a key mediator of systemic inflammation that becomes elevated in HF patients and may contribute to poor cardiac function. In animal models of HF, IL-1 is sufficient to cause significant depression of cardiac function, impaired cardiac reserve, and worsened cardiac remodeling. In a recent pilot study, 12 weeks treatment with recombinant human IL-1 receptor antagonist (IL-1Ra, anakinra) produced a significant improvement in aerobic exercise performance as measured by peak oxygen consumption (VO2). This proposal will support a randomized, double-blind, phase II clinical trial (n=102) to confirm the effect of IL-1 blockade to improve exercise capacity in HF patients and estimate the potential benefit of IL-1 blockade on HF readmission in patients with recently decompensated heart failure (HF). Eligible patients will be randomized to 24 weeks treatment with anakinra (n=68) or placebo (n=34). Results from this study will be used to optimize the treatment strategy and design a subsequent phase III clinical trial to evaluate long-term morbidity and mortality with IL-1 blockade in HF patients.

项目摘要该应用是针对单位研究者发起的临床试验（R61/R33）的题为“ 白介素-1近期致力于收缩压心力衰竭的患者的运动能力封锁” 由Antonio Abbate医学博士，博士和Benjamin van Tassell提交。心力衰竭（HF）是一个复杂的临床综合征的特征是劳累时疲劳和实验室呼吸。虽然当前的治疗期权延长了预期寿命，HF的促进性仍然很差，而HF是美国老年患者的入院。迫切需要开发新的治疗方法来减轻症状，疾病进展缓慢并减少HF住院。心脏功能下降和炎症水平增加之间存在显着的相关性 HF患者的细胞因子。在这些细胞因子中，白介素-1（IL-1）是全身的关键介体 HF患者的炎症升高，可能导致心脏功能差。在动物中 HF，IL-1的模型足以引起心脏功能严重抑郁，心脏储备受损，并恶化心脏重塑。在最近的一项试点研究中，重组人IL-1治疗12周受体拮抗剂（IL-1RA，Anakinra）在有氧运动表现方面显着改善通过峰值消耗（VO2）测量。该提案将支持一项随机，双盲，II期临床试验（n = 102），以确认效果 IL-1封锁以提高HF患者的运动能力并估算IL-1阻滞的潜在益处关于最近失去心力衰竭（HF）的患者的HF再入院。合格的患者将是用anakinra（n = 68）或安慰剂（n = 34）随机分配24周。这项研究的结果将被使用优化治疗策略并设计随后的III期临床试验以评估长期 HF患者对IL-1阻滞的发病率和死亡率。