Inhaled Mometasone to Promote Reduction in Vaso-occlusive Events (IMPROVE)

吸入莫米松可促进减少血管闭塞事件（改进）

基本信息

批准号：
9304272
负责人：
Jeffrey Avins Glassberg
金额：
$ 19.21万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-16 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9304272
关键词：
Accident and Emergency department Acute Adherence Admission activity Adolescent Adrenal Cortex Hormones Adult Affect American Asthma Attenuated Award Bayesian Analysis Biological Biological Markers Blood Vessels Breathing Caring Cessation of life Characteristics Child Clinic Clinical Clinical Trials Clinical Trials Design Coughing Data Diagnosis Dose Double-Blind Method Emergency Department Physician Emergency department visit Enrollment Event Exhalation Expenditure FDA approved Feasibility Studies Future Goals Hemoglobin Hemolysis Hypoxia Inborn Genetic Diseases Individual Inflammation Injury Institution Intervention Studies Learning Literature Logistics Lung Measures Mentors Methods Modeling Morbidity - disease rate Multicenter Trials Nitric Oxide Observational Study Outcome Outcome Measure Pain Pain-Free Participant Pathogenesis Patient Self-Report Patients Pharmaceutical Preparations Phase Physicians Placebo Control Placebos Play Preparation Principal Investigator Property Publishing Pulmonary Inflammation Randomized Randomized Controlled Trials Rare Diseases Recruitment Activity Recurrence Reporting Research Research Personnel Respiratory Signs and Symptoms Risk Risk Factors Sample Size Sampling Sickle Cell Sickle Cell Anemia Spirometry Structure Subgroup Symptoms Techniques Testing Therapeutic Therapeutic Trials Time Training United States Vascular Cell Adhesion Molecule-1 Visit Wheezing acute chest syndrome age group aged body system career clinical investigation cost design diaries health related quality of life hydroxyurea improved innovation insight meetings mortality patient oriented prevent programs research study simulation skills standard of care therapy development treatment response trend trial design vaso-occlusive pain

项目摘要

DESCRIPTION (provided by applicant): The goal of the proposed studies and structured educational plan is to develop the PI into an independent investigator with the career goal of preventing acute complications and improving emergent management of sickle cell disease (SCD), with focus on learning innovative approaches to trial design to meet challenges specific to SCD research. The Principal Investigator will receive advanced individualized and classroom training that will build upon the candidate's strengths as an emergency physician and prior training in clinical investigation to learn specific quantitative skills necessary to transition ito the next phase of his career, including adaptive trial design methods, Bayesian analysis and longitudinal modeling techniques. SCD is an inherited disorder of hemoglobin with manifestations in all organ systems. One of the greatest risk factors for vaso-occlusion and death in adolescents and adults with SCD is the presence of respiratory symptoms such as cough or wheeze. Preliminary data indicate that recurrent cough or wheeze occurs in nearly half of individuals with SCD who do not carry a physician diagnosis of asthma. The proposed research is designed to test the global hypothesis that inhaled corticosteroids (ICS), a therapy developed to treat asthma, will prevent vaso-occlusive painful episodes in adults with SCD who wheeze, but do not meet criteria for a diagnosis of asthma. The specific aims of this proposal are 1) Conduct a feasibility study - a randomized controlled trial of ICS for adults with SCD who do not meet criteria for a diagnosis of asthma but report recurrent cough or wheezing, 2) Measure the effects of ICS on biological correlates of pulmonary inflammation (as determined by exhaled nitric oxide) and vascular injury (as determined by sVCAM) in SCD, and 3) Compare properties of traditional and Bayesian adaptive clinical trial design for therapeutic trials in SCD in preparation for designing a definitive trial of ICS. These aims have the potentia to 1) change the standard of care for individuals with SCD and recurrent cough or wheeze, 2) provide insight into the pathogenesis of non-asthmatic wheezing in SCD and its response to treatment, 3) explore the suitability of innovative clinical trial designs to overcome the challenges that have hindered therapeutic innovation for SCD.

描述（由申请人提供）：拟议研究和结构化教育计划的目标是将 PI 发展为独立研究者，其职业目标是预防急性并发症和改善镰状细胞病 (SCD) 的紧急管理，重点是学习创新的试验设计方法可应对 SCD 研究的特定挑战。首席研究员将接受先进的个性化和课堂培训，这些培训将建立在候选人作为急诊医生的优势和之前的临床调查培训的基础上，以学习过渡到职业生涯下一阶段所需的具体定量技能，包括适应性试验设计方法、贝叶斯方法分析和纵向建模技术。 SCD 是一种血红蛋白遗传性疾病，可在所有器官系统中表现出来。患有 SCD 的青少年和成人血管闭塞和死亡的最大危险因素之一是出现咳嗽或喘息等呼吸道症状。初步数据表明，近一半的 SCD 患者在没有医生诊断为哮喘的情况下会出现反复咳嗽或喘息。拟议的研究旨在检验以下全球假设：吸入皮质类固醇（ICS）是一种治疗哮喘的疗法，可以预防患有喘息但不符合哮喘诊断标准的 SCD 成人患者的血管闭塞性疼痛发作。该提案的具体目标是 1) 进行可行性研究 - 针对不符合哮喘诊断标准但报告反复咳嗽或喘息的 SCD 成人进行 ICS 随机对照试验，2) 测量 ICS 对生物活性的影响SCD 中肺部炎症（由呼出的一氧化氮确定）和血管损伤（由 sVCAM 确定）的相关性，以及 3) 比较传统和贝叶斯自适应临床试验设计在 SCD 中的治疗试验的特性为设计 ICS 的最终试验做准备。这些目标有可能 1) 改变 SCD 和反复咳嗽或喘息患者的护理标准，2) 深入了解 SCD 患者非哮喘性喘息的发病机制及其对治疗的反应，3) 探索创新药物的适用性临床试验设计旨在克服阻碍 SCD 治疗创新的挑战。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inhaled steroids reduce pain and sVCAM levels in individuals with sickle cell disease: A triple-blind, randomized trial.

DOI：
10.1002/ajh.24742
发表时间：
2017-07
期刊：
American journal of hematology
影响因子：
12.8
作者：
Glassberg J;Minnitti C;Cromwell C;Cytryn L;Kraus T;Skloot GS;Connor JT;Rahman AH;Meurer WJ
通讯作者：
Meurer WJ

Bayesian analyses demonstrate tissue blood volume is not decreased during acute sickle cell pain episodes: A preliminary study.