Peripheral Artery Disease

The goal of this clinical trial is to assess the effects of passive calf muscle stretching in patients diagnosed with peripheral artery disease (PAD). The main question it aims to answer are: 1. To determine if daily calf muscle stretching at home improves calf muscle and vascular health. 2. To determine if daily calf muscle stretching at home improves walking performance. Participants will use inflatable ankle splints for 30 minutes a day, 5 days a week for 4-weeks on both days and 4-weeks of no stretching.

Lower extremity revascularization combined with supervised exercise significantly improves walking performance compared to revascularization alone in people who have PAD without limb threatening ischemia. However, supervised exercise is inaccessible or burdensome for most PAD patients. Investigators hypothesize that home-based exercise combined with lower extremity revascularization will significantly improve walking performance compared to revascularization alone in patients with PAD undergoing revascularization for disabling PAD. Investigators further hypothesize that inorganic nitrate, a major source of nitric oxide (NO) abundant in beetroot juice, will improve walking performance after lower extremity revascularization, compared to placebo. In preclinical models, NO inhibits inflammation, neointimal hyperplasia, thrombosis, and vascular smooth muscle cell migration at sites of revascularization. NO increases angiogenesis and perfusion, repairs skeletal muscle damaged by ischemia, and stimulates mitochondrial activity. In a randomized clinical trial with a 2 x 2 factorial design, the trial will test the following two primary hypotheses in 386 patients randomized within three months of a successful lower extremity revascularization for disabling PAD: First, that home-based exercise combined with lower extremity revascularization will improve six-minute walk distance more than revascularization alone at 6-month follow-up (Primary Aim #1). Second, that nitrate-rich beetroot juice combined with lower extremity revascularization will improve six-minute walk, compared to placebo combined with revascularization at 6-month follow-up (Primary Aim #2).

Peripheral artery disease can reduce blood flow to the legs. In some patients, the superficial femoral artery, a major artery in the thigh, is completely blocked over a long segment. This study will evaluate a minimally invasive treatment for these blockages. Approximately 60 adults who require endovascular treatment will undergo placement of a filter beyond the blockage to collect debris. Rotational atherectomy will then be used to remove part of the material causing the blockage, followed by drug-coated balloon angioplasty to widen the artery. A stent may be placed only if needed because of an inadequate treatment result or a procedure-related complication. Participants will be evaluated by clinical examination and duplex ultrasound at 1, 3, 6, and 12 months. The main goal is to determine how often the treated artery remains open at 12 months. The study will also evaluate technical success, the need for repeat treatment, material captured by the filter, and procedure-related blockage of smaller downstream arteries.

The primary goal of this clinical trial is to evaluate whether a community-based structured exercise therapy (CB-SET) intervention, which could be accessible and easily disseminated, adds benefit to peripheral artery disease (PAD) patients undergoing revascularization (REVASC) to improve their function and cardiovascular health.

The study aims to conduct a randomized controlled trial among adults aged 19 years or older who have experienced acute myocardial infarction at least one year prior, or who have other comorbidities such as peripheral arterial disease or multiple cardiovascular diseases, and have consented to participate in the study. Participants will be randomly assigned to either a group that maintains antiplatelet therapy with aspirin and clopidogrel or clopidogrel alone, or a group that maintains combined antiplatelet and anticoagulant therapy with aspirin and low-dose rivaroxaban in a 1:1 ratio. The study aims to demonstrate that maintaining clopidogrel-based antiplatelet therapy is not clinically inferior to maintaining combined therapy with aspirin and low-dose rivaroxaban.

To evaluate the safety and performance of the IV-X Medical Intravascular Lithotripsy (IVL) System in adults in order to demonstrate the ability of the IV-X Medical IVL System to safely and effectively deliver IVL treatment calcified peripheral arteries (iliac, femoral, ilio-femoral, popliteal, and infra-popliteal arteries).

The goal of this randomized, double-blind, sham-controlled clinical trial is to evaluate the benefits of home-based, leg heat therapy (HT) on lower-extremity functioning and quality of life in patients who suffer from lower-extremity peripheral artery disease (PAD). We will randomize 106 patients to one of two groups that either receive leg HT or a sham intervention. The primary study outcome is the change in 6-minute walk distance between baseline and the 12-week follow up. Secondary outcomes include changes in the short physical performance battery score, handgrip strength, quality of life (measured by the Walking Impairment Questionnaire and Short-Form (SF)-36 Questionnaire), calf muscle strength (measured using a calf ergometer), size (measured by magnetic resonance imaging) and bioenergetics (assessed using phosphorus-31 magnetic resonance spectroscopy), and physical activity (measured by accelerometer).

RESIST PAD is a randomized trial of 200 PAD patients to establish: 1) whether a 12-week exercise intervention significantly increases Δ nitrite at 12-week follow-up, compared to control; 2) whether exercise "responders" have greater Δ nitrite increases compared to "non-responders"; 3) among non-responders, whether supplementing exercise with nitrate-rich beetroot juice between weeks 13-24 increases Δ nitrite and improves 6-minute walk at 24-week follow-up.

Obstructive sleep apnea syndrome (OSAS) is characterized by partial (hypopnea) or complete (apnea) obstruction of the upper airways, leading to intermittent hypoxemia and sleep fragmentation. Peripheral arterial occlusive disease (PAOD) is a chronic condition defined by the narrowing or occlusion of arteries in the lower limbs, often resulting in ischemia of downstream tissues. This disease is a common complication of atherosclerosis and affects approximately 1.2% of the general French population. OSAS is a well-established risk factor for atherosclerotic disease, particularly for coronary and neurovascular events. Although a relationship between OSAS and PAOD has been investigated in recent years, the link has not been definitively established and requires further study. Therefore, this preliminary cohort study aims to observe the prevalence of OSAS among patients diagnosed with PAOD, regardless of the disease stage.

Peripheral arterial disease (PAD) is a chronic atherosclerotic condition associated with impaired mobility, reduced quality of life, cardiovascular events, and risk of lower limb amputation. Although supervised exercise therapy (SET) is recommended for symptomatic PAD, access and adherence remain limited, particularly among patients with moderate-to-severe disease or chronic limb-threatening ischemia (CLTI). The PILOT-PAD-CYCLE study is a prospective, single-center, pilot randomized controlled trial designed to evaluate the feasibility, acceptability, and preliminary efficacy of a 12-week home-based exercise therapy (HET) program using a portable pedal exerciser in adults with moderate-to-severe PAD, including CLTI, with or without foot wounds. Twelve participants will be randomized 1:1 to either HET plus standard care or standard care alone. The intervention includes individualized exercise prescription, remote supervision by a kinesiologist, cardiovascular education, and follow-up over 12 weeks. Outcomes include feasibility and acceptability metrics, 6-minute walk test distance, vascular perfusion indices, quality of life, and cardiovascular events up to 6 months. This pilot trial aims to generate feasibility data and preliminary efficacy estimates to support the development of a future multicenter randomized controlled trial.

Peripheral artery disease (PAD) is associated with elevated oxidative stress, and oxidative stress has been implicated as the cause of reduced endothelial reactivity in individuals with PAD. Endothelial function is important because the endothelium contributes to the dilation of arteries during exercise, thereby implicating impaired endothelial function as a mechanism contributing to exacerbated exercise-induced ischemia. Therefore, the purpose of this study is to test the hypothesis that acute exogenous diroximel fumarate (Vumerity) intake will improve antioxidant capacity, thereby reducing oxidative stress and improving vascular function and walking capacity in those with PAD. During this study, participants will be administered diroximel fumarate or a placebo, and the acute effects of diroximel fumarate on vascular function and walking capacity will be assessed. Vascular function and walking capacity will be assessed with flow-mediated dilation, arterial stiffness, head-up tilt test, blood biomarkers, near-infrared spectroscopy, and a treadmill test. There will be a follow-up visit to assess blood work after diroximel fumarate.

This single-center, 400-patient, randomized controlled trial assesses the impact of a patient- and provider-facing EPIC Best Practice Advisory (BPA; alert-based computerized decision support tool) to increase guideline-directed utilization of statin and statin-alternative oral LDL-C lowering therapies in patients with PAD who are not being prescribed LDL-C-lowering therapy.

Peripheral artery disease (PAD), vascular disease of atheromatous origin, is a frequent pathology, with a steady and significant increase in prevalence over the last decades. It has various symptoms ranging from mild arterial claudication to critical limb ischemia. The critical ischaemia stage in PAD is defined by rest pain or trophic disorders and is a special situation because of the number of cardiovascular deaths at 1 year (25%), 60% at 5 years and acute ischaemic recurrence at 1 year (25%). It is a medico-surgical pathology. A haemodynamic marker is needed to monitor patients, as it is predictive of limb progression, cardiovascular events and mortality. The Systolic Rise Time (SRT) of the plantar footpad is a recently described haemodynamic measurement of proven value in the diagnosis of PAD. The aim of this study is to show the prognostic value of the Systolic Rise Time on Major Adverse Limb Events (MALE).

The goal of this clinical trial is to test the Thor system in adult (≥ 18 year old) patients with de novo (new, never treated) calcified lesions in infrainguinal (leg) arteries (peripheral artery disease or PAD). The main question\[s\] it aims to answer are: * Is the Thor system safe in treating these lesions * Does the Thor system work to treat these lesions Participants will: * Receive treatment with the Thor system * Have follow-up visits at Discharge, 30 days, 6 months, and 12 months

This study is a 3-month, prospective, randomized controlled clinical trial designed to address the efficacy of the Non-Ischemic Exercise (NICE) program to improve exercise and vascular outcome measures in patients with peripheral artery disease (PAD).

Among people with peripheral artery disease (PAD) age 55 and older, the investigators will test the hypothesis that PAD participants randomized to cocoa flavanols will have greater improvement or less decline in six-minute walk distance at six-month follow-up, compared to those randomized to placebo. The study will randomize 190 participants with PAD age 55 and older to one of two groups for six months: cocoa flavanols vs placebo. Our primary outcome is change in six-minute walk distance at six-month follow-up. Secondary outcomes are Actigraph-measured physical activity, brachial artery flow-mediated dilation (FMD), gastrocnemius muscle biopsy measures of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, gastrocnemius muscle perfusion (measured by magnetic resonance imaging (MRI)) and gastrocnemius muscle characteristics (measured by muscle biopsy). To achieve the specific aims, the study will randomize 190 participants age 55 and older with PAD to one of two groups: cocoa flavanols vs placebo. Participants will be followed for six months.

Peripheral artery disease (PAD) is a chronic atherosclerotic disorder characterized by stenosis or occlusion of the extracranial arteries distal to the aortic arch, most commonly affecting the lower extremities. This vascular compromise leads to tissue hypoperfusion, resulting in a spectrum of clinical manifestations ranging from asymptomatic disease to intermittent claudication, critical limb ischemia, and limb loss. The microvascular system comprises arterioles, capillaries, and post-capillary venules with diameters less than or equal to 100 micrometers. Emerging evidence underscores that microvascular dysfunction (MVD)-defined as structural and functional impairment of this microcirculatory network-plays a pivotal pathophysiological role in PAD progression, contributing to impaired perfusion reserve, endothelial dysfunction, inflammation, and tissue fibrosis, independent of macrovascular stenosis severity. Super-resolution ultrasound microvascular imaging (SRUMI) is an advanced contrast-enhanced ultrasound technique that leverages the nonlinear acoustic signatures of intravascular microbubble contrast agents (e.g., SonoVue) under ultra-low mechanical index (MI) pulsing schemes. Implemented on the Verasonics Vantage 256 research platform (Verasonics, Inc., Kirkland, WA, USA), SRUMI achieves in vivo visualization of microvascular architecture at sub-diffraction resolution (approximately 10-20 micrometers), surpassing conventional Doppler and contrast-enhanced ultrasound. Key advantages include absence of ionizing radiation, negligible thermal and mechanical bioeffects, real-time capability, portability, and cost-effectiveness. As such, SRUMI represents a promising noninvasive tool to probe microvascular integrity in PAD, enabling mechanistic investigation of MVD's contribution to disease initiation, progression, and therapeutic response. This study aims to evaluate the diagnostic and prognostic utility of SRUMI for assessing microvascular dysfunction in patients with PAD. The investigators prospectively enrolled patients diagnosed with PAD and admitted to the Department of Interventional Vascular Surgery at Peking University First Hospital. Primary objectives include: Characterizing lower-limb microvascular density, morphology, and perfusion patterns via SRUMI across PAD subgroups stratified by comorbidities-including diabetes mellitus, current or former smoking, hypertension, and chronic kidney disease; Assessing the concordance between SRUMI-derived microvascular parameters and established clinical and paraclinical markers, including symptom severity (Rutherford classification), ankle-brachial index (ABI), urinary albumin-to-creatinine ratio (UACR), and retinal microvascular findings on fundoscopy; Determining the sensitivity, specificity, and predictive value of baseline SRUMI metrics for major adverse limb events (MALE) and cardiovascular outcomes during longitudinal follow-up; and Comparing the incremental prognostic value of SRUMI against conventional modalities-including ABI, duplex ultrasonography, and clinical risk scores-using multivariable Cox regression and time-dependent receiver operating characteristic (ROC) analyses. Collectively, this research seeks to establish SRUMI as a quantitative, translatable biomarker of microvascular health in PAD, thereby advancing precision phenotyping, risk stratification, and monitoring of therapeutic efficacy in this high-morbidity population.

The objective of this first-in-human study is to assess the safety and effectiveness of the Serranator Sonic Intravascular Lithotripsy (IVL) System™ for the treatment of peripheral artery disease.

Walking is beneficial for adults with peripheral arterial disease. Benefits include the ability to walk for longer periods and general well being (quality of life). This study will look at two types of delivery methods for a home-based walking program. The walking program includes step count goals, information on healthy walking and motivational messages. The two delivery methods include a web-based delivery and an telehealth delivery. Participants are randomized to either one of the delivery methods or usual care. After 12 weeks participants in the web based or telehealth based groups maybe re-randomized to receive a combination of both web-based and telehealth for a second 12 week period. After 24 weeks, everyone is followed for an additional 12 weeks, so the total time a participant is in the study is 36 weeks. At baseline, 12, 24 and 36 weeks the investigators ask participant to walk (slowly) on a treadmill, perform a six-minute walk test, and several questionnaires on quality of life. Vouchers are provided at each study visit. All participants who complete the study also keep their pedometer.

To compare the efficacy and safety of stent angioplasty with Orchid 035 Drug Coated Dilatation (DCB) and Plain Old Balloon Angioplasty (POBA) for post-dilatation for long (\>10cm) femoropopliteal chronic total occlusion.

To assess the rates of ischemic and hemorrhagic complications of long-term antithrombotic therapy in patients with chronic coronary syndromes

Subjects with a known diagnosis of peripheral artery disease as measured by an abnormal ankle brachial index (\<.9 or \>1.1) will undergo a single 5 min exposure of 670 nm light, 1 cm above the gastrocnemius muscle. Blood flow will be measured by infusion of ultrasound contrast and subsequent acquisition of ultrasound images. 2 blood samples will be collected for measurement of nitric oxide metabolites.

This study is a 3-month, prospective, randomized controlled clinical trial designed to address the efficacy of the DASH dietary program combined with a home-based exercise program, quantified by a step activity monitor, to improve exercise and vascular outcome measures in patients with PAD.

The ENLIGHTEN PAD Trial will collect preliminary data to test whether daily 660 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 people with lower extremity peripheral artery disease (PAD).

The BEET PAD Trial is a multi-centered double-blind randomized clinical trial designed to determine whether beetroot juice, compared to placebo, improves six-minute walk distance at four month follow-up in people with lower extremity peripheral artery disease (PAD). Investigators hypothesize that by simultaneously increasing lower extremity perfusion, gastrocnemius muscle mitochondrial activity, and myofiber health and regeneration, beetroot juice will significantly improve walking performance in people with PAD. The primary aim is to determine whether beetroot juice significantly improves six-minute walk distance at 4-month follow-up in people with PAD, compared to placebo. Preliminary evidence suggests that beetroot juice has both acute and chronic effects on walking performance in PAD. The primary outcome will measure the combined acute and chronic effect of beetroot juice (i.e. the maximal effect) on change in 6-minute walk at 4-month follow-up. In secondary aims, investigators will distinguish between acute and chronic effects of beetroot juice on six-minute walk and delineate biologic pathways by which beetroot juice improves walking performance in PAD, by measuring change in gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health. The trial will assess the durability of beetroot juice effects on six-minute walk. Nitrate in beetroot juice is metabolized to nitrite and subsequently to NO, attaining peak nitrite levels 2.5 hours after ingestion. The trial will determine whether a higher peak or a greater increase in plasma nitrite at 2.5 hours after beetroot juice consumption at baseline has a greater effect on six-minute walk at 4-month follow-up, compared to a lower peak or a smaller increase, respectively.