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）

• 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
• 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

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(申请人提供)：拟议的研究和结构化教育计划的目标是将PI发展成为一名独立的研究人员，其职业目标是预防急性并发症和改善镰状细胞病(SCD)的紧急处理，重点是学习试验设计的创新方法，以应对SCD研究的特定挑战。首席调查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先前的临床调查培训的基础上，以学习过渡到其职业生涯下一阶段所需的具体量化技能，包括适应性试验设计方法、贝叶斯分析和纵向建模技术。SCD是一种遗传性的血红蛋白疾病，表现在所有的器官系统。在患有SCD的青少年和成人中，血管闭塞和死亡的最大危险因素之一是出现呼吸道症状，如咳嗽或喘息。初步数据表明，在没有被医生诊断为哮喘的SCD患者中，近一半会出现反复咳嗽或喘息。这项拟议的研究旨在检验全球假设，即吸入皮质类固醇(ICS)是一种治疗哮喘的疗法，将防止患有哮喘但不符合哮喘诊断标准的成人SCD患者发生血管闭塞疼痛发作。这项建议的具体目的是1)对不符合哮喘诊断标准但报告反复咳嗽或喘息的成人SCD患者进行ICS的可行性研究-ICS的随机对照试验，2)测量ICS对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)的生物相关性的影响，以及3)比较SCD治疗试验的传统和贝叶斯适应性临床试验设计的特性，为设计ICS的最终试验做准备。这些目标有可能1)改变SCD和反复咳嗽或喘鸣患者的护理标准，2)为SCD中非喘息性喘息的发病机制及其治疗反应提供洞察，3)探索创新临床试验设计的适用性，以克服阻碍SCD治疗创新的挑战。

项目成果

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.

• DOI: 10.3233/ch-141927
• 发表时间: 2016
• 期刊: Clinical hemorheology and microcirculation
• 影响因子: 2.1
• 作者: Perry M;Simon J;Gareau D;Glassberg J
• 通讯作者: Glassberg J