Far Red Light to Improve Functioning in PAD: the LIGHT PAD Trial

远红光改善 PAD 功能：LIGHT PAD 试验

• 批准号: 10572758
• 负责人: Mary McGrae McDermott
• 金额: $ 26.76万
• 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: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572758
• 关键词: Acute; Affect; Age; Animal Model; Biological; Biological Availability; Biopsy; Blood capillaries; Blood flow; Cell Nucleus; Chronic; Clinical Trials; Data; Devices; Disabled Persons; Dose; Elderly; Gastrocnemius Muscle; Health; Home; Hour; Human; Impairment; Intervention; Ischemia; Leg; Light; Lower Extremity; Magnetic Resonance Imaging; Measures; Mitochondria; Muscle; Muscle Fibers; Muscle Mitochondria; Nitric Oxide; Nitrites; Outcome; Oxidative Stress; Participant; Pathology; Pathway interactions; Patient Outcomes Assessments; Patients; Performance; Perfusion; Peripheral arterial disease; Persons; Phase; Phototherapy; Pilot Projects; Plasma; Preparation; Property; Quality of life; Questionnaires; Randomized; Reperfusion Injury; Signaling Molecule; Skeletal Muscle; Source; Testing; Therapeutic; Vascular Endothelial Growth Factors; Walking; Woman; Work; angiogenesis; arterial spin labeling; density; design; disability; enzyme activity; follow-up; functional decline; functional disability; functional improvement; human old age (65+); improved; ischemic injury; limb ischemia; men; phase II trial; pre-clinical; preclinical study; prevent; primary outcome; randomized trial; randomized, clinical trials; repaired; satellite cell; secondary outcome; treadmill

Far Red Light to Improve Functioning in PAD: the LIGHT PAD Trial Lower extremity peripheral artery disease (PAD) affects 10-15% of people age 65 and older and 15 to 20% of those age 75 and older. Older people with PAD have greater functional impairment, faster functional decline, and higher rates of mobility loss than people without PAD. In PAD, reduced perfusion of gastrocnemius muscle is associated with increased gastrocnemius oxidative stress, mitochondrial impairment, and muscle fiber damage. Yet few non-invasive therapies improve functioning in people with PAD. Nitric oxide (NO) is a signaling molecule with therapeutic properties that improve perfusion and reverse the skeletal muscle pathology in PAD. In preclinical studies, NO increases angiogenesis and perfusion, protects against ischemic injury, enhances skeletal muscle mitochondrial activity, and activates satellite cells, which restore and repair skeletal muscle. Interventions that increase NO bioavailability have major therapeutic potential for people with PAD. Nitrosothiols are a major source of NO and NO bioactivity. Preclinical studies and our preliminary human evidence show that far red light (at wavelength of 670 nm) releases nitrosothiols, nitrite, and other vasoactive species. Four pilot studies completed in preparation for this proposal showed that a single dose of far red light therapy increased plasma nitrosothiols, improved lower extremity blood flow, and meaningfully improved functional performance in people with PAD. Therefore, we propose a Phase II randomized clinical trial to collect preliminary data to test whether four months of daily far red light treatment of the lower extremities improves walking performance, lower extremity perfusion, and ischemia-related gastrocnemius muscle damage in people with PAD, compared to a sham control. Thirty- two people with PAD will be randomized to 10 minutes of daily home treatment with either far red light or a sham light for four months. Our primary outcome is change in six-minute walk distance at 4- month follow-up. In secondary and exploratory aims, we will distinguish between acute and chronic effects of far red light on six-minute walk, measure the effects of far red light on treadmill walking performance and patient-reported outcomes, and delineate biologic pathways by which far red light improves walking performance in PAD, by measuring change in plasma nitrite and nitrosothiols, gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health and mitochondrial activity (measured by muscle biopsy). If our hypotheses are supported by this Phase II trial, results will be used to design a definitive randomized trial of far red light for people with PAD. If far red light improves functional performance in PAD, this simple, accessible, and well tolerated therapy will have a major impact on preventing mobility loss and improving quality of life in the large and growing number of older people disabled by PAD.

远红光改善PAD功能：LIGHT PAD试验 下肢外周动脉疾病（PAD）影响10-15%的65岁及以上人群，15 - 20%的65岁及以上人群， 75岁及以上的人。老年PAD患者功能障碍更大，功能障碍更快， 下降，以及比没有PAD的人更高的行动能力丧失率。在PAD中， 腓肠肌与腓肠肌氧化应激，线粒体损伤， 和肌肉纤维损伤。然而，很少有非侵入性疗法改善PAD患者的功能。 一氧化氮（NO）是一种具有治疗特性的信号分子，可改善灌注并逆转心肌缺血。 PAD中的骨骼肌病理学。在临床前研究中，NO增加血管生成和灌注， 抗缺血性损伤，增强骨骼肌线粒体活性，激活卫星细胞， 恢复和修复骨骼肌。增加NO生物利用度的干预措施具有主要的治疗作用。 对于PAD患者的潜力。 亚硝基硫醇是NO和NO生物活性的主要来源。临床前研究和我们的初步人类 有证据表明，远红光（波长为670 nm）会释放亚硝基硫醇、亚硝酸盐和其他血管活性物质， 物种为准备这项提议而完成的四项试点研究表明，单剂量的远红光 治疗增加血浆亚硝基硫醇，改善下肢血流量，并有意义地改善 PAD患者的功能表现。 因此，我们建议进行一项II期随机临床试验，以收集初步数据，以测试四种 月的日常远红光治疗的下肢改善行走性能，下肢 灌注和缺血相关的腓肠肌损伤，与假手术相比， 控制32名PAD患者将随机接受10分钟的每日家庭治疗， 红灯或假灯四个月。我们的主要结果是在4- 月随访。在次要和探索性目标中，我们将区分急性和慢性效应， 远红光对6分钟步行的影响，测量远红光对跑步机步行表现的影响， 患者报告的结果，并描绘远红光改善行走的生物学途径 通过测量血浆亚硝酸盐和亚硝基硫醇的变化，腓肠肌灌注， (MRI动脉自旋标记）和腓肠肌肌肉健康和线粒体活性（通过肌肉自旋标记测量 活组织检查）。如果我们的假设得到II期试验的支持，结果将用于设计一个确定的 远红光治疗PAD患者的随机试验。如果远红光改善了PAD的功能性能， 这种简单、容易获得且耐受性良好的疗法将对预防活动能力丧失产生重大影响， 改善因PAD致残的大量且不断增加的老年人的生活质量。