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.

顺序多重评估锻炼的随机试验：PAD的智能锻炼 监督运动疗法（SET），由跑步机运动组成3次/周的中心进行 在医疗保健人员的面前，下肢是为残疾人残疾人的第一线治疗 动脉疾病（PAD）。但是，前往场景的中心很繁重。截至2018年，只有1.3％ 患有Medicare和有症状垫的患者已入学。家庭锻炼更容易获得 比设定少的朴素。但是，指南建议将基于家庭的锻炼设置为垫子。 临床试验已经确定了基于家庭运动干预措施的三个特征 对PAD的人有效：1）纳入行为改变方法； 2）与教练定期接触 3）运动强度，在运动过程中引起缺血腿症状。最近我们报道了Jama 基于家庭的锻炼干预措施，包括这些特征 与注意力控制组相比，在PAD中改进了6分钟的步行路程。但是，没有随机试验有 直接将设置为对有垫的人进行高效的家庭运动干预。此外， 有45％的垫子的人对运动没有有意义的反应，被定义为无法改善六分钟的步行 距离> 20米（临床上有意义的改进）。这两个现象都是针对两者的监督 和家庭锻炼。我们的II期试验表明，富含硝酸盐的甜菜根汁，增加了血浆 亚硝酸盐，肢体灌注和运动强度，显着降低了运动的无响应速率， 与安慰剂相比，在垫子中。因此，我们将使用顺序多重评估随机试验 （SMART）解决两个主要障碍，以使PAD的锻炼受益：首先，建议 监督运动。其次，缺乏在PAD中进行无反应运动的治疗方法。 在智能练习中，有250名带垫的参与者将被随机分为家庭锻炼或 设置12周（第一阶段）。在12周的随访中，参与者将分为“响应者”（> 20米 步行6分钟或“非反应者”（步行6分钟步行<20米）的改善。在第13周中 24（第二阶段），所有参与者将继续其最初分配的运动状况（设置或基于家庭）， 并将无反应者重新随机以用甜菜根汁或安慰剂加强 继续他们的原始练习。我们将检验两个主要假设。首先，无论我们的家庭 运动干预措施比在12周的随访中改善了6分钟的步行路程（主要目的＃1）。第二， 甜菜根汁的锻炼生物学增强是否可以改善PAD患者的6分钟步行 12周后不反应运动（主要目的＃2）。在中学和探索目的中，我们将确定 最佳的运动策略，以最大程度地提高所有PAD患者的步行距离，从而 改善了数以百万计的老年人的流动性。