Sequential Multiple Assessment Randomized Trial of Exercise for PAD: SMART Exercise for PAD

PAD 运动的序贯多重评估随机试验：PAD 的 SMART 运动

• 批准号: 10584209
• 负责人: Mary McGrae McDermott
• 金额: $ 72.31万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584209
• 关键词: Address; Beets; Behavioral; Biological; Characteristics; Clinical; Clinical Trials; Control Groups; Disabled Persons; Elderly; Enrollment; Exercise; Exercise Therapy; Exercise Tolerance; Failure; Guidelines; Health Personnel; Home; Impairment; Isolated limb perfusion; Juice; Leg; Lower Extremity; Measures; Medicare; Methods; Muscle function; Nitrates; Nitrites; Participant; Patients; Performance; Peripheral arterial disease; Persons; Placebos; Plant Roots; Plasma; Practice Guidelines; Randomized; Recommendation; Reporting; Research Design; Skeletal Muscle; Supervision; Symptoms; Testing; Time; Travel; Walking; Work; attentional control; base; evidence based guidelines; exercise intensity; exercise intervention; follow-up; improved; improved mobility; meter; optimal treatments; phase II trial; randomized trial; responders and non-responders; standard of care; treadmill; trial design

Sequential Multiple Assessment Randomized Trial of Exercise for PAD: SMART Exercise for PAD Supervised exercise therapy (SET), consisting of treadmill exercise conducted 3 times/week at a center in the presence of healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling to a center for SET is burdensome. As of 2018, only 1.3% of patients with Medicare and symptomatic PAD had enrolled in SET. Home-based exercise is more accessible and less burdensome than SET. Yet, guidelines recommend SET over home-based exercise for PAD. Clinical trials have identified three characteristics of home-based exercise interventions that are highly effective for people with PAD: 1) incorporation of behavioral change methods; 2) regular contact with a coach, and 3) an exercise intensity that elicits ischemic leg symptoms during exercise. Recently we reported in JAMA that a home-based exercise intervention that included these characteristics significantly and meaningfully improved 6-minute walk in PAD, compared to an attention control group. However, no randomized trials have directly compared SET to a highly effective home-based exercise intervention for people with PAD. In addition, 45% of people with PAD do not meaningfully respond to exercise, defined as failure to improve six-minute walk distance by > 20 meters (a clinically meaningful improvement). This phenomenon occurs for both supervised and home-based exercise. Our Phase II trial showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and exercise intensity, significantly reduced rates of non-response to exercise, compared to placebo, in PAD. Therefore, we will use a Sequential Multiple Assessment Randomized Trial (SMART) to address two major barriers to benefit from exercise for PAD: First, the recommendation for supervised exercise. Second, the lack of treatment for non-response to exercise in PAD. In SMART Exercise for PAD, 250 participants with PAD will be randomized to home-based exercise or SET for 12 weeks (Stage I). At 12-week follow-up, participants will be classified into ‘responders’ (> 20 meter improvement in 6-minute walk) or ‘non-responders’ (< 20 meter improvement in 6-minute walk). In weeks 13- 24 (Stage II), all participants will continue their originally assigned exercise condition (SET or home-based), and non-responders will be re-randomized to either augmentation with beetroot juice or placebo while continuing their original exercise. We will test two primary hypotheses. First, whether our home-based exercise intervention improves 6-minute walk more than SET at 12-week follow-up (Primary Aim #1). Second, whether biologic augmentation of exercise with beetroot juice improves 6-minute walk in PAD patients unresponsive to exercise after 12 weeks (Primary Aim #2). In Secondary and Exploratory Aims, we will identify the optimal exercise strategy to maximize gains in walking distances for all patients with PAD, thereby improving mobility in the millions of older people disabled by PAD.

PAD 运动的序贯多重评估随机试验：PAD 的 SMART 运动 监督运动疗法 (SET)，包括每周在中心进行 3 次跑步机运动 在医护人员在场的情况下，是下肢末梢损伤患者的一线治疗 然而，截至 2018 年，只有 1.3% 的患者需要前往 SET 中心就诊。 参加 SET 的 Medicare 和有症状的 PAD 患者更容易进行家庭锻炼。 而且比 SET 负担更轻，然而，指南建议针对 PAD 进行 SET 锻炼，而不是在家进行锻炼。 临床试验已经确定了家庭运动干预的三个特征，这些特征非常有效。 对 PAD 患者有效：1) 结合行为改变方法；2) 定期与教练联系， 3) 最近我们在《美国医学会杂志》上报道了在运动过程中引起腿部缺血症状的运动强度。 包含这些特征的家庭运动干预措施显着且有意义 与注意力对照组相比，PAD 患者的 6 分钟步行有所改善。但是，尚无随机试验表明。 直接将 SET 与针对 PAD 患者的高效家庭运动干预进行了比较。 45% 的外周动脉疾病 (PAD) 患者对运动没有任何有意义的反应，定义为未能改善六分钟步行 距离> 20 米（具有临床意义的改善）。 我们的第二阶段试验表明，富含硝酸盐的甜菜根汁可以增加血浆。 亚硝酸盐、肢体灌注和运动强度，显着降低运动无反应率， 与安慰剂相比，在 PAD 中，我们将使用序贯多重评估随机试验。 （SMART）旨在解决 PAD 患者从锻炼中获益的两大障碍：首先，建议 其次，缺乏对 PAD 运动无反应的治疗。 在针对 PAD 的 SMART 锻炼中，250 名患有 PAD 的参与者将被随机分配到家庭锻炼或 SET 为期 12 周（第一阶段）。在 12 周的随访中，参与者将被分为“响应者”（> 20 米）。 6 分钟步行改善）或“无反应”（6 分钟步行改善 < 20 米）。 24日（第二阶段），所有参与者将继续他们原来指定的锻炼条件（SET或在家）， 无反应者将被重新随机分配至甜菜根汁或安慰剂增强组，同时 我们将测试两个主要假设：首先，我们是否以家庭为基础。 在 12 周的随访中，运动干预比 SET 改善了 6 分钟步行（主要目标 1）。 使用甜菜根汁进行生物强化运动是否可以改善 PAD 患者的 6 分钟步行能力 12 周后对运动没有反应（主要目标 #2）。在次要目标和探索性目标中，我们将确定。 最佳锻炼策略可最大限度地增加所有 PAD 患者的步行距离，从而 改善数百万因 PAD 致残的老年人的活动能力。