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Feasibility and Safety of Interleukin-1 Blockade to Treat Cardiac Sarcoidosis

IL-1 阻断治疗心脏结节病的可行性和安全性

基本信息

批准号：
9890056
负责人：
Antonio Abbate
金额：
$ 22.62万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9890056
关键词：
Address Adrenal Cortex Hormones Affect African American American Heart Association Anti-Inflammatory Agents Architecture Arrhythmia Attenuated Biological Markers C-reactive protein Cardiac Cardiac Electrophysiologic Techniques Cardiac Sarcoidosis Cardiomyopathies Cardiovascular Diseases Cardiovascular system Cessation of life Clinical Clinical Trials Collaborations Complex Controlled Clinical Trials Country Data Diagnosis Diagnostic Disease Double-Blind Method Event Functional disorder Future Granuloma Granulomatous Health Heart Heart Diseases Heart failure Human Inflammasome Inflammation Inflammatory Inflammatory Response Interleukin-1 Interleukin-1 Receptors Interleukin-6 International Kineret Lead Leadership Life Literature Liver Lung Measures Michigan Minority Molecular Monitor Myocardial Myocardial Ischemia Myocarditis Natural History Organ Outcome Patients Pharmaceutical Preparations Phase Pilot Projects Placebos Plasma Population Heterogeneity Predictive Value Protein Biosynthesis Recombinant Interleukin-1 Registries Research Research Personnel Research Proposals Resources Role Sarcoidosis Severity of illness Societies Steroids Subgroup Surrogate Endpoint Sweden Testing Tissues Translating Translational Research Universities Virginia Woman Work adverse outcome anakinra base body system cardioprotection chronic inflammatory disease clinical application clinical care cytokine design effective therapy heart rhythm improved improved outcome innovation interest member novel novel therapeutics phase 3 study pre-clinical pre-clinical research randomized placebo-controlled clinical trial recruit response safety and feasibility side effect standard care targeted treatment therapy development translational scientist

项目摘要

SUMMARY Sarcoidosis is an inflammatory disease that can affect any organ system. Rarely, sarcoidosis can affect the heart, leading to life-threatening heart rhythm problems, heart failure, and death. There are no drugs specifically approved for the treatment of sarcoidosis. Remarkably, despite >50 years of use as the most common therapy for sarcoidosis, there is no proof that corticosteroid treatment works for cardiac sarcoidosis. Preliminary data indicate a role for interleukin-1, the prototypical cytokine, in granuloma formation in sarcoidosis and we have shown evidence of IL-1 inflammasome formation in cardiac tissue of patients with cardiac sarcoidosis. Clinical trials have shown that IL-1 blockers can improve outcomes in ischemic heart disease and heart failure. Our research seeks to evaluate whether IL-1 blockade with the IL-1 receptor antagonist, anakinra, can safely modulate systemic inflammation in patients with active cardiac sarcoidosis. IL- 1 blockade is a novel therapeutic strategy that has not been tested in cardiac sarcoidosis. We have designed a double-blind randomized placebo-controlled clinical trial of anakinra, an IL-1 receptor blocker, given for 4 weeks in 28 patients with cardiac sarcoidosis. We will determine feasibility of recruitment and tolerability of treatment with anakinra in cardiac sarcoidosis patients and determine the effects of anakinra on systemic inflammation as measured by C reactive protein and IL-6, inflammatory biomarkers shown to be surrogates for cardiovascular outcomes. The study will build on the collaboration of two CTSA hubs that are international leaders in cardiac sarcoidosis clinical care – Virginia Commonwealth University and the University of Michigan, under the translational research leadership of Dr. Antonio Abbate, an expert in cardiac inflammation. This proposal addresses urgent unmet needs that are common to both the National Center for Advancing Translational Sciences (NCATS) and the American Heart Association (AHA) - defined as the need of translating biomedical discoveries into clinical applications to improve human health and specifically of developing therapies to attenuate disease impact of cardiac sarcoidosis – a condition for which no targeted therapy exists. The results of this pilot study will serve as proof-of-concept data to conceive future phase III studies involving CTSA hubs across the country. A novel targeted treatment could bring about a much-needed paradigm shift in the treatment of cardiac sarcoidosis.

总结