Aspirin before Exercise: Antipyretic pretreatment to reduce exercise-induced overheating and exhaustion in RRMS patients

运动前服用阿司匹林：退热预处理可减少 RRMS 患者运动引起的过热和疲惫

• 批准号: 9908128
• 负责人: VICTORIA M LEAVITT
• 金额: $ 20.25万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908128
• 关键词: Academic Medical Centers; Acetaminophen; Achievement; Adoption; Adult; Anaerobic Threshold; Anti-Inflammatory Agents; Aspirin; Attenuated; Bathing; Behavioral; Biophysics; Blood Pressure; Body Temperature; Brain-Derived Neurotrophic Factor; Clinical; Clinical Research; Cognition; Data; Disabled Persons; Dose; Double-Blind Method; Drops; Enrollment; Ensure; Exercise; Exercise Test; Exertion; Fatigue; Funding; Future; Goals; Grant; Hand; Health; Hour; Ice; Individual; Knowledge; Lead; Link; Measures; Modeling; Moods; Multiple Sclerosis; Myelin; Oral Administration; Outcome; Participant; Patients; Performance; Persons; Phase; Physical Function; Physical activity; Placebos; Pre-Clinical Model; Productivity; Property; Quality of life; Ramp; Relapse; Relapsing-Remitting Multiple Sclerosis; Reporting; Research; Research Project Grants; Rest; Risk; Sampling; Schedule; Secondary to; Serum; Societies; Standardization; Symptoms; Temperature; Testing; Time; VO2max; Vacuum; Work; antipyretic; arm; axon injury; base; capsule; chronic neurologic disease; clinical care; cost effective; design; disability; effective therapy; exercise adherence; exhaustion; experience; experimental study; improved; multiple sclerosis patient; neural model; novel; patient oriented research; physical symptom; pilot trial; primary outcome; recruit; secondary outcome; success

As indicated by NCMRR, the primary goal of patient-oriented research is to develop the “scientific knowledge necessary to enhance the health, productivity, independence, and quality- of-life of people with disabilities.” Multiple sclerosis (MS) is a prevalent and chronic neurologic disease that impacts individuals on many levels. Exercise holds a multitude of benefits for persons with MS (PwMS), including improved physical function, reduced fatigue, improved mood, and improved cognition. There is now evidence from pre-clinical models for neural-level benefits of exercise including increased BDNF, and reduced myelin and axonal damage. But exercise only works if people do it, and many PwMS are deterred from exercising by overheating, exhaustion, and symptom worsening: “Uhthoff’s phenomenon.” Our group extended Uhthoff’s observation by providing the first-ever report of elevated resting body temperature and its link to worse fatigue in persons with MS; that is, even before exercise, PwMS are already “heated up.” This R21 will support a trial of aspirin as a pretreatment for exercise: our pilot data collected in 12 participants show improved exercise performance and reduced exercise-induced body temperature increase after aspirin. For the proposed study, sixty MS patients will be enrolled in a double-blind RCT with three arms: placebo, aspirin, and acetaminophen (APAP). Design is crossover: each participant will complete three exercise sessions separated by 1-week intervals. At each session, body temperature will be measured before administration of a standard adult dose (two 325-mg capsules) of aspirin, APAP, or placebo. One hour later (time to reach peak serum level) participants will complete a progressive ramped maximal exercise test on a lower body cycle ergometer. Body temperature and biophysical/behavioral variables (VO2max, total watts achieved, blood pressure, anaerobic threshold, ratings of perceived exertion) will be recorded throughout the test at regular intervals. Past research in MS has found cooling treatments (cooling garments, vacuum hand-cooling chambers) effective for improving exercise performance. However, their widespread adoption for research / clinical use is limited by practicality and lack of standardization. Aspirin is a simple, readily available, cost-effective treatment that does not require FDA approval. If successful, this R21 grant may motivate change in clinical care and adoption of ASA therapy for enhancing exercise performance in PwMS. Positive findings from this study will facilitate future research to test whether ASA use improves exercise adherence, increases everyday physical activity levels, and improves overall QOL for persons with MS.

正如NCMRR所指出的，以患者为导向的研究的主要目标是开发 “提高健康、生产力、独立性和质量所必需的科学知识- 残疾人的生活”。多发性硬化症（MS）是一种流行的慢性神经系统疾病， 疾病会在多个层面上影响个体。锻炼对身体有很多好处， MS患者（PwMS），包括身体功能改善、疲劳减轻、 改善情绪和认知。现在有证据表明，从临床前模型的神经水平 运动的好处包括增加BDNF，减少髓鞘和轴突损伤。但 锻炼只有在人们这样做的情况下才有效，许多PwMS被阻止锻炼， 过热、疲劳和症状恶化：“Uhthoff现象”。我们集团 通过提供有史以来第一份关于静止身体升高的报告， 温度及其与MS患者更严重疲劳的联系;也就是说，即使在运动之前， PwMS已经“升温”。这项R21将支持阿司匹林作为治疗前的试验， 运动：我们在12名参与者中收集的试验数据显示，运动表现有所改善， 减少阿司匹林后运动引起的体温升高。在研究报告中，60 MS患者将入组一项双盲RCT，分为三组：安慰剂、阿司匹林和阿司匹林。 对乙酰氨基酚（APAP）。设计是交叉的：每个参与者将完成三个练习 会议间隔1周。在每一次会议上，将测量体温 在给予标准成人剂量（2粒325 mg胶囊）阿司匹林、APAP或 安慰剂一小时后（达到峰值血清水平的时间），参与者将完成一项 在下半身自行车测力计上进行渐进式斜坡最大运动试验。体温 和生物物理/行为变量（最大摄氧量、达到的总瓦特数、血压、无氧 阈值、感知用力的等级）将在整个测试中定期记录。 过去在MS的研究发现，冷却治疗（冷却服装，真空手冷却 室）有效地改善运动表现。然而，它们的广泛采用 用于研究/临床使用的方法受到实用性和缺乏标准化的限制。阿司匹林是一 简单，易得，具有成本效益的治疗方法，不需要FDA批准。如果 如果成功，R21拨款可能会推动临床护理的变化和阿萨治疗的采用， 提高PwMS中的运动表现。这项研究的积极结果将有助于未来 一项研究旨在测试阿萨的使用是否能提高锻炼的坚持性， 活动水平，并改善MS患者的整体QOL。

项目成果

ASPIRE trial: study protocol for a double-blind randomised controlled trial of aspirin for overheating during exercise in multiple sclerosis.

• DOI: 10.1136/bmjopen-2020-039691
• 发表时间: 2020-11-14
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Kever A;Nelson KE;Aguerre IM;Riley CS;Boehme A;Lee NW;Strauss Farber R;Levin SN;Stein J;Leavitt VM
• 通讯作者: Leavitt VM