Cerebrovascular Disease in Sickle Cell Anemia

描述(由申请人提供)：候选人-勒纳博士是一名儿科血液学家/肿瘤学家，最近将她的重点转向了以患者为中心的研究。她已经完成了公共卫生硕士学位的课程工作，并与罗切斯特大学医学中心的经验丰富的临床研究人员建立了工作关系。 环境-医疗中心拥有经验丰富的临床研究人员和必要的资源，以确保勒纳博士的成功。特别是，一个咨询委员会将为这项提议提供支持。临床试验协调中心和STRONG儿童研究中心将提供更多的专业知识。 研究--脑血管疾病继发的神经系统并发症在患有纯合子镰状细胞病的儿童中很常见。据推测，每天小剂量的阿司匹林治疗将安全地减少这些儿童认知障碍的发生率和进展，以及对显性和静止性中风的易感性。为了最大限度地设计未来的第三阶段试验来检验这一假设，NINDS已经批准了一项先导性研究。其主要目的是评估阿司匹林的安全性和耐受性。这项K24申请提出了额外的研究，以扩大试验。这些研究将探讨炎症和凝血的实验室标记物与脑血管损伤的发生和进展的预后关系。随后的研究将评估阿司匹林治疗后那些具有预测能力的实验室参数的变化。后来提出的研究包括关于有记录的中风儿童的磁共振成像的调查，关于慢性输液治疗的调查，以及为改善神经认知缺陷儿童的表现而量身定做的教育修改。 指导-首席研究员将为对儿科脑血管疾病、血红蛋白疾病和/或神经认知功能特别感兴趣的合格MD提供临床研究培训。受训人员将从以下人员中招募：儿科血液学/肿瘤学研究员、公共卫生硕士(临床跟踪)候选人、神经内科课程参与者和住院医生。该计划将包括核心教育指导、系列研讨会和个性化指导。受训人员将参加试点试验和多中心第三阶段研究的进行，如果有资金的话。本申请中建议的其他研究将作为最初的个人临床研究机会。将使用结果衡量标准来评估指导计划的效果。

DESCRIPTION (provided by applicant): Candidate - Dr. Lerner is a pediatric hematologist/oncologist who has recently redirected her focus to patient-oriented investigation. She has completed the course work for an MPH degree and has established working relationships with experienced clinical investigators at the University of Rochester Medical Center. Environment -The Medical Center has the experienced clinical researchers and requisite resources to ensure Dr. Lerner's success. In particular, a Consultant Committee will provide support for this proposal. The Clinical Trials Coordinating Center and Strong Children's Research Center will lend additional expertise. Research - Neurologic complications secondary to cerebrovascular disease are prevalent in children with homozygous sickle cell disease. It is hypothesized that daily low-dose aspirin therapy will safely diminish the incidence and progression of cognitive deficit as well as the predisposition to overt and silent stroke in these children. In order to maximize the design of a future Phase III trial to test this hypothesis, a pilot study has been approved by the NINDS. Its primary objective is to evaluate the safety and tolerability of aspirin. This K24 application proposes additional studies to augment the trial. These will investigate the prognostic relationship of laboratory markers of inflammation and coagulation to the incidence and progression of cerebrovascular damage. Subsequent investigations will evaluate the change secondary to aspirin therapy in those laboratory parameters with prognostic capability. Later proposed studies include investigations regarding magnetic resonance imaging in children with documented stroke on chronic transfusion therapy and tailored educational modifications to improve performance in children with neurocognitive deficits. Mentorship -The principle investigator will provide clinical research training to qualified MDs with a particular interest in pediatric cerebrovascular disease, hemoglobinopathies, and/or neurocognitive function. Trainees will be recruited from: Pediatric Hematology/Oncology fellows, Masters in Public Health (clinical track) candidates, participants in programs of the Department of Neurology, and residents. The program will include core educational instruction, seminar series, and individualized guidance. Trainees will participate in the conduct of the pilot trial and a multi-center phase III study, should this be funded. The additional studies proposed in this application will serve as initial individual clinical research opportunities. Outcome measures will be used to assess the efficacy of the mentoring program.