Leg Exercise Assistive Paddling (LEAP) Therapy for Peripheral Artery Disease

Обзор

The purpose of this study is to test the effects of leg exercise assistive paddling (LEAP) therapy during prolonged sitting (PS) on vascular and functional performance in those with peripheral artery disease (PAD) and age-matched controls. LEAP therapy is a novel application of passive limb movement to enhance blood flow through the legs without muscular contractions. Specifically, LEAP therapy is the rotational passive movement of the lower leg about the knee from 90 to 180 degrees of rotation at a cadence of 1Hz. Previous literature has indicated that this movement pattern can produce robust increases in blood flow in the passively moved limb in healthy individuals, and passive limb movement may protect vascular function during PS. However, the impact of LEAP therapy to improve blood flow in the legs of those with PAD during PS is unknown. Participants will participate in a randomized cross-over design study with 2 visits (LEAP therapy and no LEAP therapy). For the first visit, participants will be randomly allocated to receive LEAP therapy during 2.5 hours of PS or not. For the second visit, participants will sit for 2.5 hours and will receive the condition that they did not previously receive. Before and after PS, the following measurements will be made: flow-mediated dilation of the popliteal and brachial arteries, arterial stiffness with tonometry techniques, microvascular vasodilatory capacity and skeletal muscle metabolic rate with near-infrared spectroscopy, autonomic nervous system function, and there will be blood drawn from the antecubital vein. After PS, participants will participate in a graded exercise test to assess functional walking capacity. Finally, during PS, near-infrared spectroscopy on the calf muscles and electrocardiogram will be collected continuously to monitor muscle oxygen availability and autonomic activity, respectively.

Подробное описание

Epidemiological studies suggest that over 200 million adults worldwide currently have peripheral artery disease (PAD), which is the buildup of atherosclerotic plaques in the arteries of the legs and is associated with high rates of morbidity and mortality. The population most suspectable to PAD is older adults, with the incidence of PAD increasing exponentially after the age of 50. This sharp age demarcation makes PAD particularly concerning for Western societies, where the proportion of older adults is steadily rising, thereby making PAD a large potential future burden to healthcare systems and economies alike. Therefore, the discovery and development of interventions to prevent and treat PAD is a top biomedical concern that has a high future return on investments.

Exercise and physical activity are known to improve functional capacity in those with PAD. In fact, exercise therapies have been reported to be as effective as revascularization surgeries at restoring functional walking capacity. However, despite the major benefits of exercise, adherence to supervised exercise therapies is low, and those with PAD report being highly sedentary, which is likely attributed to the muscle pain they experience during exercise. Elevated sedentarism among those with PAD is concerning, since the investigators and others have demonstrated that sedentarism in the form of prolonged sitting (i.e., sitting for \>1 hour) can 1) increase arterial stiffness, 2) reduce the vasodilatory capacities of the macro- and micro-vasculatures, 3) reduce skeletal muscle metabolism, and 4) reduce shear stress in the large conduit arteries, all of which are known to promote atherosclerosis. Importantly, since those with PAD already demonstrate impaired vascular function, they may be more suspectable to the negative effects of prolonged sitting on vascular health. Remarkably, the investigators have shown that passive movement of the legs (i.e., limb movement without active muscle contractions) can prevent vascular decline during prolonged sitting. Therefore, passive limb movement (PLM) therapies may be an effective strategy to provide light physical activity to those with PAD and protect them against the deleterious effects of sedentarism. Importantly, since PLM does not require active skeletal muscle work, it is likely that PLM will be well-tolerated by those with PAD, and adherence to PLM therapies may be enhanced compared to traditional exercise. Therefore, developing methods that mimic exercise with PLM may be an effective front-line strategy to improve functional capacity, vascular function, and quality of life in those with PAD.

Unfortunately, there are currently no available methods that provide PLM therapy for those with PAD, and it is not known whether PLM therapies can protect the vasculature of those with PAD during PS. Therefore, the investigators have developed the Leg Exercise Assistive Paddling (LEAP) protocol to provide PLM therapy during PS. LEAP therapy is a standardized protocol for those with PAD that provides PLM by rotating the lower leg about the knee from 90-180° at a cadence of 1Hz for 1 minute every 10 minutes. These parameters have been chosen for LEAP therapy because of the robust increases in leg blood flow elicited by these parameters. The investigators hypothesize that LEAP therapy prevents vascular and functional decline in those with PAD during PS. Therefore, the development and validation of LEAP therapy is expected to promote PLM therapies as a new interventional strategy to improve vascular and functional capacities in those with PAD.

Participants will participate in a randomized cross-over design study with 2 visits (LEAP therapy and no LEAP therapy). For the first visit, participants will be randomly allocated to receive LEAP therapy during 2.5 hours of PS or not. For the second visit, participants will sit for 2.5 hours and will receive the condition that they did not previously receive. Before and after PS, the following measurements will be made: flow-mediated dilation of the popliteal and brachial arteries, arterial stiffness with tonometry techniques, microvascular vasodilatory capacity and skeletal muscle metabolic rate with near-infrared spectroscopy, autonomic nervous system function, and there will be blood drawn from the antecubital vein. After PS, participants will participate in a graded exercise test to assess functional walking capacity. Finally, during PS, near-infrared spectroscopy on the calf muscles and electrocardiogram will be collected continuously to monitor muscle oxygen availability and autonomic activity, respectively.

Вмешательства

• Другое LEAP therapy
  Knee bending from 90°-180° at 1Hz for 1 minute every 10 minutes during 2.5 hours of prolonged sitting
• Другое no LEAP therapy
  2.5 hours of uninterrupted prolonged sitting (no movement)

Первичные конечные точки

• Macrovascular Endothelial Function [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]
• Microvascular Vasodilatory Capacity [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]
• Femoral and Popliteal Artery Blood Flow [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]
• Walking capacity [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]
• Autonomic Function [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]
• Autonomic Activity [Срок оценки: Day 1: during the condition. Day 7: during the condition]
• Arterial Stiffness [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]
• Muscle Oxygenation [Срок оценки: Day 1: during the condition. Day 7: during the condition]
• Peripheral blood mononuclear cell mitochondrial function [Срок оценки: Day 1: before and after condition. Day 7: before and after condition.]

Критерии участия

Критерии включения

PAD subjects:

• Able to provide written informed consent
• 50-85 years of age
• Diagnosed with Peripheral Arterial Disease (PAD) Fontaine stage II-III
• Women must be postmenopausal (cessation of menses for > 24 months)
• History of exercise-induced claudication
• Free of ulcers, gangrene, or necrosis of the foot, Fontaine stage IV PAD

Age-matched control subjects:

• Able to provide written informed consent
• 50-85 years of age
• No evidence of peripheral occlusive disease, ankle-brachial index > 0.90
• Women must be postmenopausal (cessation of menses for > 24 months)

Критерии исключения

PAD subjects:

• Pain at rest and/or tissue loss from Peripheral Arterial Disease (PAD), Fontaine stage IV PAD
• Acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
• Limited walking capacity from conditions other than PAD
• Have not had a physical exam to assess exercise limitations in the past year
• Pregnant or nursing
• Kidney disease or type II diabetes mellitus

Age-matched control subjects:

• Positive diagnosis of Peripheral Arterial Disease (PAD)
• Any exercise limitations as determined at last physical exam, at least 1 year prior to study
• Have not had a physical exam to assess exercise limitations in the past year
• Limited walking capacity from musculoskeletal injury
• Pregnant or nursing
• Kidney disease or type II diabetes mellitus

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Nebraska - Omaha — Omaha

Публикации

• Song P, Rudan D, Zhu Y, Fowkes FJI, Rahimi K, Fowkes FGR, Rudan I. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health. 2019 Aug;7(8):e1020-e1030. doi: 10.1016/S2214-109X(19)30255-4. PMID 31303293
• Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006 Aug 15;114(7):688-99. doi: 10.1161/CIRCULATIONAHA.105.593442. No abstract available. PMID 16908785
• Matsushita K, Sang Y, Ning H, Ballew SH, Chow EK, Grams ME, Selvin E, Allison M, Criqui M, Coresh J, Lloyd-Jones DM, Wilkins JT. Lifetime Risk of Lower-Extremity Peripheral Artery Disease Defined by Ankle-Brachial Index in the United States. J Am Heart Assoc. 2019 Sep 17;8(18):e012177. doi: 10.1161/JAHA.119.012177. Epub 2019 Sep 10. PMID 31500474
• Allison MA, Armstrong DG, Goodney PP, Hamburg NM, Kirksey L, Lancaster KJ, Mena-Hurtado CI, Misra S, Treat-Jacobson DJ, White Solaru KT; American Heart Association Council on Peripheral Vascular Disease; Council on Hypertension; and Council on Lifestyle and Cardiometabolic Health. Health Disparities in Peripheral Artery Disease: A Scientific Statement From the American Heart Association. Circulati PMID 37317860
• Kohn CG, Alberts MJ, Peacock WF, Bunz TJ, Coleman CI. Cost and inpatient burden of peripheral artery disease: Findings from the National Inpatient Sample. Atherosclerosis. 2019 Jul;286:142-146. doi: 10.1016/j.atherosclerosis.2019.05.026. Epub 2019 May 27. PMID 31170647
• Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the Ame PMID 27840332
• Regensteiner JG, Steiner JF, Hiatt WR. Exercise training improves functional status in patients with peripheral arterial disease. J Vasc Surg. 1996 Jan;23(1):104-15. doi: 10.1016/s0741-5214(05)80040-0. PMID 8558725
• McDermott MM, Dayanidhi S, Kosmac K, Saini S, Slysz J, Leeuwenburgh C, Hartnell L, Sufit R, Ferrucci L. Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease. Circ Res. 2021 Jun 11;128(12):1851-1867. doi: 10.1161/CIRCRESAHA.121.318242. Epub 2021 Jun 10. PMID 34110902

Идентификаторы

NCT: NCT06389149 · 0165-24-FB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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