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
本申请是一项由调查员发起的名为“Effect of”的临床试验
白介素1阻断近期失代偿性收缩心力衰竭患者的运动能力
作者:Antonio Abbate,医学博士和Benjamin Van Tassell,制药博士。心力衰竭(HF)是一种复杂的疾病
以劳累和劳累时呼吸困难为特征的临床综合征。尽管目前的治疗方法
选择延长了预期寿命,心力衰竭的预后仍然很差,心力衰竭是导致
美国老年患者的入院情况。迫切需要开发新的治疗方法来缓解
症状,延缓疾病进展,减少心力衰竭住院时间。
心功能下降与炎症水平升高之间存在显著的相关性
心衰患者的细胞因子。在这些细胞因子中,白介素1(IL-1)是系统性红斑狼疮的关键介质。
炎症在心力衰竭患者中升高,可能导致心功能不佳。在动物身上
模型的HF,IL-1足以引起心功能的显著抑制,心脏储备受损,
并加重心脏重塑。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)可显著提高有氧运动成绩
以最大耗氧量(VO2)衡量。
这项建议将支持一项随机、双盲、II期临床试验(n=102)以确认疗效。
IL-1阻断改善心力衰竭患者运动能力及评价IL-1阻断的潜在益处
近期失代偿性心力衰竭(心衰)患者再次入院的情况。符合条件的患者将是
随机接受阿纳金拉(n=68)或安慰剂(n=34)治疗24周。这项研究的结果将被用于
优化治疗策略并设计后续的III期临床试验,以评估长期疗效
IL-1阻断治疗心力衰竭患者的发病率和死亡率。
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
-
项目类别:
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资助金额:$0.7万
-
财政年份:2020
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负责人:Antonio Abbate
-
依托单位:
Unconventional IL-1 signaling in heart failure
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批准号:10356119
-
项目类别:
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资助金额:$38.81万
-
财政年份:2020
-
负责人:Antonio Abbate
-
依托单位:
Unconventional IL-1 Signaling in Heart failure
-
批准号:10829159
-
项目类别:
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资助金额:$38.11万
-
财政年份:2020
-
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:
-
资助金额:$26.5万
-
财政年份:2020
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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: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:
-
资助金额:$57.27万
-
财政年份:2018
-
负责人:Antonio Abbate
-
依托单位:
Interleukin-1 blockade in acute myocardial infarction
-
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
-
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