ENhancing exercise with LIGHT to improve functioning in PAD: the ENLIGHTEN PAD Trial

利用 LIGHT 加强锻炼以改善 PAD 功能：ENLIGHTEN PAD 试验

• 批准号: 10645929
• 负责人: Mary McGrae McDermott
• 金额: $ 26.75万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645929
• 关键词: Accelerometer; Acute; Age; Biological; Biopsy; Blood capillaries; Cell Nucleus; Chronic; Citrate (si)-Synthase; Clinical Trials; Control Groups; Data; Disabled Persons; Dose; Elderly; Exercise; Gastrocnemius Muscle; Health; Home; Impairment; Intervention; Ischemia; Isolated limb perfusion; Leg; Light; Light Exercise; Lower Extremity; Magnetic Resonance Imaging; Measures; Mitochondria; Muscle; Muscle Fibers; Nitric Oxide; Nitrites; Outcome; Participant; Pathology; Pathway interactions; Perfusion; Peripheral arterial disease; Persons; Phototherapy; Plasma; Property; Quality of life; Questionnaires; Randomized; Reporting; Signaling Molecule; Skeletal Muscle; Source; Symptoms; Testing; Therapeutic; Walking; actigraphy; arterial spin labeling; comparison control; cytochrome c oxidase; density; design; disability; exercise adherence; exercise intensity; exercise intervention; follow-up; functional improvement; improved; improved mobility; light effects; meter; phase II trial; randomized trial; satellite cell

ENhancing exercise with LIGHT to improve functioning in PAD: the ENLIGHTEN PAD Trial Walking exercise is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, walking exercise does not eliminate disability due to PAD. Even after completing one of our successful exercise interventions that meaningfully improved six-minute walk distance, 82% of 192 PAD participants still reported ischemic leg symptoms after the six-minute walk. Our LITE randomized trial of 305 people with PAD showed that, compared to a control group that did not exercise, home-based walking exercise that induced ischemic leg symptoms (i.e. high intensity) significantly improved six-minute walk, while home- based exercise that did not induce ischemic leg symptoms (i.e. low intensity) had no effect on six-minute walk. Despite greater benefits, ischemic leg symptoms during high intensity exercise reduced exercise adherence. We hypothesize that 670 nm light therapy, administered before home-based walking exercise, will increase minutes of high intensity exercise and enhance the benefits of exercise in PAD. Nitric oxide (NO) is an endogenous signaling molecule with therapeutic properties that improve limb perfusion and reverses the skeletal muscle pathology present in PAD. 670 nm light treatment of the lower extremities increases plasma nitrosothiols, a major source of NO activity. In our preliminary study, 670 nm light treatment of the legs acutely increased lower extremity arterial flow and six-minute walk distance in people with PAD. Therefore, we hypothesize that 670 nm light treatment of the legs immediately before walking exercise sessions will acutely increase nitrosothiols and NO and facilitate greater exercise intensity, thereby enhancing the chronic benefits of exercise in people with PAD. The ENLIGHTEN PAD Trial will collect preliminary data to test whether, in people with PAD, daily 670 nm light treatment of the lower extremities immediately before home-based walking exercise sessions improves six-minute walk distance at 4-month follow-up, compared to sham light. In primary aim #1, we will test whether 670 nm light + home-based exercise increases six-minute walk distance more than sham light + home-based exercise at 4-month follow-up. In primary aim #2, we will measure the acute effect of the first treatment of 670 nm light on six-minute walk distance and on walking intensity (measured with the ActiGraph accelerometer) during the six-minute walk. In secondary and exploratory aims, we will delineate biologic pathways by which 670 nm light enhances the benefits of walking exercise, by measuring the effects of 670 nm light on plasma nitrosothiols, leg perfusion, and gastrocnemius muscle health. If our hypotheses are correct, we will use results of this Phase II Trial to design a definitive clinical trial to test whether 670 nm light, a safe, accessible, and well-tolerated therapy, enhances the benefits of exercise, thereby improving mobility and quality of life in the large and growing number of older people disabled by PAD.

加强LIGHT锻炼以改善PAD功能：ENLIGHTEN PAD试验 步行锻炼是下肢外周动脉疾病（PAD）致残者的一线治疗方法。 然而，步行锻炼并不能消除PAD造成的残疾。即使在完成了我们的 成功的运动干预，有意义地改善了6分钟步行距离，82%的192 PAD 参与者在步行6分钟后仍然报告腿部缺血症状。我们的LITE随机试验305 PAD患者显示，与不锻炼的对照组相比， 引起腿部缺血症状（即高强度）的药物显著改善了6分钟步行，而回家- 不引起缺血性腿部症状（即低强度）的运动对6分钟步行没有影响。 尽管有更大的益处，但高强度运动期间的腿部缺血症状降低了运动坚持性。 我们假设，在家庭步行锻炼前进行670 nm光治疗， 分钟的高强度运动，增强运动对PAD的益处。 一氧化氮（NO）是一种内源性信号分子，具有改善肢体功能的治疗特性， 灌注和逆转PAD中存在的骨骼肌病理。670 nm光治疗下 四肢增加血浆亚硝基硫醇，NO活性的主要来源。在我们的初步研究中，670 nm 腿部的轻度治疗急性增加了下肢动脉血流量和6分钟步行距离 关于PAD因此，我们假设，670 nm光治疗的腿立即步行前， 运动会急剧增加亚硝基硫醇和NO，促进更大的运动强度，从而 增强PAD患者运动的长期益处。 ENLIGHTEN PAD试验将收集初步数据，以测试PAD患者是否每天670 nm 在家庭步行锻炼之前立即对下肢进行轻度治疗， 在4个月随访时，与假光照相比，6分钟步行距离。在主要目标#1中，我们将测试是否 670 nm光+家庭锻炼比假光+家庭锻炼增加6分钟步行距离 4个月随访时进行锻炼。在主要目标#2中，我们将测量670的首次治疗的急性效应。 nm光对6分钟步行距离和步行强度的影响（使用ActiGraph加速计测量） 在六分钟的步行中。在次要和探索性目标中，我们将描绘生物学途径， 通过测量670 nm光对血浆的影响， 亚硝基硫醇、腿部灌注和腓肠肌健康。如果我们的假设是正确的，我们将使用 这项II期试验的结果是设计一项明确的临床试验，以测试670 nm光，一种安全，可获得， 和耐受性良好的治疗，增强了运动的益处，从而提高了运动的灵活性和生活质量， 因PAD而致残的老年人数量庞大且不断增加。