The PREVENTABLE Physical Performance Ancillary Study

可预防的身体表现辅助研究

• 批准号: 10366941
• 负责人: Denise Kathryn Houston
• 金额: $ 52.73万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366941
• 关键词: Activities of Daily Living; Admission activity; Affect; Age; Aging; Ancillary Study; Anti-Inflammatory Agents; Antioxidants; Cholesterol; Chronic; Clinical; Clinical Research; Clinical Trials Design; Cognition; Coronary heart disease; Data; Dementia; Elderly; Equilibrium; Evaluation; Event; Fatigue; Gait speed; Health; Health Personnel; Heart failure; Infrastructure; Lead; Lipids; Lower Extremity; Measures; Muscle; Muscle Weakness; Myalgia; Myocardial Infarction; Nursing Homes; Observational Study; Outcome; Pain; Parents; Participant; Patient Recruitments; Patient Self-Report; Patient-Focused Outcomes; Patients; Performance; Peripheral arterial disease; Physical Function; Physical Performance; Physical activity; Placebos; Pragmatic clinical trial; Property; Quality of life; Randomized; Randomized Controlled Trials; Reporting; Resources; Risk; Series; Site; Stroke; Symptoms; System; Testing; Therapeutic; Time; United States Department of Veterans Affairs; Walking; aged; aging population; atorvastatin; cost effective; design; disability; effective therapy; experience; follow-up; functional decline; immunoregulation; improved; meter; middle age; mortality; multiple chronic conditions; muscle form; patient oriented; patient population; physically handicapped; preservation; prevent; side effect; symptom treatment; treatment arm; treatment group; treatment guidelines

Project Summary/Abstract Aging is associated with significant declines in muscle mass, strength, and physical performance, which often lead to disability, loss of independence, and adverse clinical outcomes including multimorbidity and mortality. At present, health care providers have no therapeutic options to offer their patients to slow aging-related declines in physical function. Importantly, evidence is emerging that statins could be an effective treatment for preserving physical function by preventing disabling events such as stroke, heart failure, or myocardial infarction. In addition, statins have pleiotropic properties including anti-inflammatory, anti-oxidant, and immuno- modulatory effects, which may slow or prevent aging-related declines in physical function. However, reports of muscle pain and weakness in patients on statins has led to a significant number of patients discontinuing statins. Thus, the proposed study is critical to establish whether statins may help to preserve physical function and independence in older adults, or whether statin-associated muscle symptoms portend a statin-related decline in physical function. The PREVENTABLE trial (U19 AG065188) provides an ideal opportunity to definitively determine the effect of statins as a treatment for aging-related declines in physical function. PREVENTABLE is a placebo-controlled pragmatic clinical trial designed to investigate whether randomization to a statin can prevent dementia and prolong disability-free survival in 20,000 participants aged 75+ years without clinically evident coronary heart disease. While the PREVENTABLE trial will help clarify the effects of statins on self-reported disability, the proposed ancillary study will extend and validate the physical disability data by investigating the effects of statins on changes in physical performance, which are typically observed earlier in the trajectory of functional decline and may be a more sensitive marker for the effects of statin. To determine if statins affect longitudinal change in physical performance, the proposed ancillary will add the Short Physical Performance Battery (SPPB), a validated measure of lower-extremity performance comprised of balance tasks, a 4-m walk, and repeated chair stand test, over 3 years of follow-up in 2,500 PREVENTABLE participants (1,250 per intervention arm). Self-reported information on patient-centered outcomes relevant to physical function including statin-associated muscle symptoms, fatigue, and pain will also be collected. The specific aims of this ancillary study are to: 1) determine whether randomization to statin slows the aging- related decline in usual gait speed; 2) determine whether randomization to statin slows aging-related declines in lower-extremity function (SPPB score) and strength (chair rise time); and 3) explore whether randomization to statin is associated with self-reported statin-associated muscle symptoms, fatigue, and pain. By leveraging the rich resources and infrastructure of PREVENTABLE, this timely and cost-effective study provides a unique opportunity to significantly expand the scope and impact of the parent trial on self-reported physical disability by determining the therapeutic potential of statins to slow aging-related declines in physical performance.

项目总结/摘要 衰老与肌肉质量、力量和身体表现的显著下降有关，这通常 导致残疾、丧失独立性和不良临床结果，包括多发性硬化和死亡。 目前，卫生保健提供者没有治疗选择，为他们的病人提供减缓衰老相关的 身体机能下降。重要的是，有证据表明他汀类药物可能是一种有效的治疗方法， 通过预防中风、心力衰竭或心肌梗塞等致残事件来保护身体功能 梗塞此外，他汀类药物具有多效性，包括抗炎、抗氧化和免疫调节。 调节作用，这可能会减缓或防止与衰老相关的身体功能下降。然而，据报道， 服用他汀类药物的患者出现肌肉疼痛和无力， 他汀类因此，拟议的研究对于确定他汀类药物是否有助于保护身体功能至关重要 和独立性，或者他汀类药物相关的肌肉症状是否预示着他汀类药物相关的 身体机能下降。可预防试验（U19 AG 065188）提供了一个理想的机会， 明确确定他汀类药物作为治疗衰老相关的身体功能下降的效果。 PREVENTABLE是一项安慰剂对照的实用临床试验，旨在研究随机化是否 他汀类药物可以预防痴呆症并延长20，000名75岁以上参与者的无残疾生存期 没有明显的冠心病虽然预防试验将有助于阐明 他汀类药物对自我报告的残疾，拟议的辅助研究将扩大和验证身体残疾 通过调查他汀类药物对身体表现变化的影响来获得数据，这些变化通常被观察到， 在功能下降的轨迹中更早，并且可能是他汀类药物作用的更敏感的标志物。到 确定他汀类药物是否影响身体机能的纵向变化，拟定的辅助治疗将增加 短体力活动成套测验（SPPB），一种经验证的下肢功能测量方法，包括 平衡任务、4米步行和重复椅子站立试验，在2，500例可预防患者中随访3年以上 参与者（每个干预组1，250人）。自我报告的以患者为中心的结局信息， 还将收集身体功能，包括他汀类药物相关的肌肉症状、疲劳和疼痛。的 该辅助研究的具体目的是：1）确定随机化至他汀类药物是否延缓衰老- 通常步态速度的相关下降; 2）确定随机化至他汀类药物是否减缓衰老相关下降 下肢功能（SPPB评分）和力量（椅子上升时间）; 3）探讨是否随机化 与自我报告的他汀类药物相关的肌肉症状、疲劳和疼痛有关。通过利用 丰富的资源和基础设施的预防，这一及时和具有成本效益的研究提供了一个独特的 有机会显著扩大父母试验对自我报告身体残疾的范围和影响 通过确定他汀类药物在减缓与衰老相关的身体机能下降方面的治疗潜力。