The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
批准号:
10449103
负责人:
Antonio Abbate
金额:
$57.34万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-07-01 至 2024-06-30
关键词:
Activities of Daily LivingAcuteAdmission activityAerobic ExerciseAldosteroneAngiotensin IIAnimal ModelAnti-Inflammatory AgentsBlood VesselsBreathingCardiacCardiopulmonaryClinicalClinical TrialsComplexCouplingDataDiagnosisDiseaseDisease MarkerDisease ProgressionDoctor of PharmacyDoctor of PhilosophyDoppler EchocardiographyDouble-Blind MethodEFRACEventExertionFatigueFingersFunctional disorderHeart failureHospitalizationHospitalsHumanImpairmentIncidenceInflammationInflammatoryInterleukin-1InterruptionKnowledgeLife ExpectancyMeasuresMediator of activation proteinMorbidity - disease rateMyocardialNorepinephrineOutcomeOxygenOxygen ConsumptionPathway interactionsPatientsPerformancePharmacologyPhasePhase II Clinical TrialsPhase III Clinical TrialsPilot ProjectsPlacebosPlayPlethysmographyPrevalencePrognosisQuality of lifeRandomizedRecombinantsRelaxationReportingResearch PersonnelRisk FactorsRoleSiteStrokeSymptomsSyndromeSystolic heart failureTestingWorkadjudicationadverse outcomeanakinracardiac depressioncostcytokinedesigndisease natural historyexercise capacityfollow-upfunctional disabilityheart functionhemodynamicshospital readmissionhuman old age (65+)improvedmortalitynovelnovel therapeutic interventionolder patientpressureprimary endpointreadmission ratesreduce symptomssecondary endpointsystemic inflammatory responsetherapy designtreatment optimizationtreatment strategyuptake
中文摘要
项目摘要
本申请是针对一项名为“研究者启动的单中心临床试验(R61/R33)的影响”的申请。
白细胞介素-1阻滞剂对近期失代偿收缩性心力衰竭患者运动能力的影响
由Antonio Abbate医学博士和Benjamin货车Tassell药学博士提交。心力衰竭(HF)是一种复杂的
一种临床综合症,特征是劳累时呼吸困难。虽然目前的治疗
选择延长了预期寿命,HF的预后仍然很差,HF是
在美国,老年患者中。迫切需要开发新的治疗方法来缓解
症状,减缓疾病进展,并减少HF住院治疗。
心功能下降与炎症反应水平升高之间存在显著相关性。
HF患者中的细胞因子。在这些细胞因子中,白细胞介素-1(IL-1)是全身性炎症的关键介质,
在HF患者中炎症升高,可能导致心脏功能不良。在动物
HF模型,IL-1足以引起心脏功能的显著抑制,心脏储备受损,
心脏重塑恶化在最近的初步研究中,用重组人IL-1治疗12周,
受体拮抗剂(IL-1 Ra,阿那白滞素)产生了显着改善有氧运动性能,
用峰值耗氧量(VO 2)来衡量。
该提案将支持一项随机、双盲、II期临床试验(n=102),以确认其效果
IL-1阻断剂改善HF患者的运动能力,并评估IL-1阻断剂的潜在益处
近期失代偿性心力衰竭(HF)患者的HF再入院。符合条件的患者将被
随机分为阿那白滞素组(n=68)和安慰剂组(n=34),治疗24周。本研究的结果将用于
优化治疗策略,并设计后续的III期临床试验,以评估长期
IL-1阻断对HF患者发病率和死亡率的影响。
英文摘要
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.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
Prevention of heart failure with IL-1 blockade: a mechanistic study
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批准号:10390821
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项目类别:
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资助金额:$64.07万
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财政年份:2022
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负责人:Antonio Abbate
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依托单位:
Prevention of heart failure with IL-1 blockade: a mechanistic study
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批准号:10577771
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项目类别:
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资助金额:$62.08万
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财政年份:2022
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负责人:Antonio Abbate
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依托单位:
Feasibility and Safety of Interleukin-1 Blockade to Treat Cardiac Sarcoidosis
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批准号:9890056
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项目类别:
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资助金额:$22.62万
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财政年份:2020
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负责人:Antonio Abbate
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依托单位:
Unconventional IL-1 signaling in heart failure
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批准号:10560648
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项目类别:
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资助金额:$0.7万
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财政年份:2020
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负责人:Antonio Abbate
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依托单位:
Unconventional IL-1 signaling in heart failure
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批准号:10356119
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项目类别:
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资助金额:$38.81万
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财政年份:2020
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负责人:Antonio Abbate
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依托单位:
Unconventional IL-1 Signaling in Heart failure
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批准号:10829159
-
项目类别:
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资助金额:$38.11万
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财政年份:2020
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负责人:Antonio Abbate
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依托单位:
Feasibility and Safety of Interleukin-1 Blockade to Treat Cardiac Sarcoidosis
-
批准号:10078287
-
项目类别:
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资助金额:$26.5万
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财政年份:2020
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负责人:Antonio Abbate
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依托单位:
The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
-
批准号:9760411
-
项目类别:
-
资助金额:$54.71万
-
财政年份:2018
-
负责人:Antonio Abbate
-
依托单位:
The Effects of Interleukin-1 Blockade On Exercise Capacity In Patients With Recently Decompensated Systolic Heart Failure
-
批准号:10222756
-
项目类别:
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资助金额:$57.27万
-
财政年份:2018
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负责人:Antonio Abbate
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依托单位:
Interleukin-1 blockade in acute myocardial infarction
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批准号:8623428
-
项目类别:
-
资助金额:$21.41万
-
财政年份:2014
-
负责人:Antonio Abbate
-
依托单位:
Interleukin-1 blockade in acute myocardial infarction
-
批准号:8866465
-
项目类别:
-
资助金额:$21.29万
-
财政年份:2014
-
负责人:Antonio Abbate
-
依托单位:
Interleukin-1 blockade in heart failure with preserved ejection fraction
-
批准号:8637318
-
项目类别:
-
资助金额:$34.31万
-
财政年份:2014
-
负责人:Antonio Abbate
-
依托单位:
Protection from Radiation Induced Cardiomyopathy
-
批准号:8692681
-
项目类别:
-
资助金额:$15.63万
-
财政年份:2013
-
负责人:Antonio Abbate
-
依托单位:
Interleukin-1 blockade in recently decompensated heart failure
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批准号:8725731
-
项目类别:
-
资助金额:$34.03万
-
财政年份:2013
-
负责人:Antonio Abbate
-
依托单位:
Interleukin-1 blockade in recently decompensated heart failure
-
批准号:8583175
-
项目类别:
-
资助金额:$33.05万
-
财政年份:2013
-
负责人:Antonio Abbate
-
依托单位:
Protection from Radiation Induced Cardiomyopathy
-
批准号:8589054
-
项目类别:
-
资助金额:$19.44万
-
财政年份:2013
-
负责人:Antonio Abbate
-
依托单位:
海外基金