Clinical Research Directory

Improving Mobility After Revascularization in Peripheral Artery Disease

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).

Exercise Therapy for PAD Using Mobile Health

Peripheral artery disease (PAD) is a highly prevalent condition affecting up to 10% of Veterans that leads to loss of walking ability and increased risk of amputation. Veterans have limited access to supervised exercise therapy, a facility-based program proven to improve walking ability in PAD, which is poorly attended due to the inconvenience and cost of attending a 12-week program with multiple weekly sessions. This CDA-2 application will investigate the feasibility of home-based exercise therapy (HBET) delivered using mobile health (mHealth) technologies in Veterans with symptomatic PAD. We will partner with the MOVE! program to deliver HBET through group behavioral coaching and a novel wearable activity monitor in a newly proposed program called Smart MOVE!. There is a clear need to provide effective and convenient alternatives to supervised exercise for Veterans with PAD. This study will provide evidence to proceed with Smart MOVE!, a much-needed patient-centered rehabilitation program for Veterans with PAD.

Passive Calf Stretching Therapy in 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.

Intermittent Pneumatic Compression With and Without Exercise to Improve Functioning in Peripheral Artery Disease

The INTERCEDE randomized trial will establish whether six-months of intermittent pneumatic compression combined with walking exercise improves walking endurance at six-month follow-up, compared to walking exercise + sham compression therapy, in people with lower extremity peripheral artery disease (PAD). The INTERCEDE trial will also determine whether intermittent pneumatic compression therapy improves walking endurance at 6-month follow-up, compared to a sham compression therapy. The trial will also determine whether benefits of intermittent pneumatic compression persist after intermittent pneumatic compression treatment is completed.

Promote Weight Loss in Obese Peripheral Artery Disease (PAD) Patients to Prevent Mobility Loss

The PROVE Trial is a randomized clinical trial that will determine whether a weight loss intervention combined with walking exercise achieves greater improvement or less decline in six-minute walk distance at 12 month follow-up than walking exercise alone in people with PAD and BMI\>25 kg/m2. The intervention uses a Group Mediated Cognitive Behavioral framework, connective mobile technology, remote monitoring by a coach, and a calorie restricted Dietary Approaches to Stop Hypertension (DASH)-derived Optimal Macronutrient Intake Trial for Heart Health (OMNIHeart) diet. 212 participants with PAD and BMI \> 25 kg/m2 will be randomized to one of two groups: weight loss + exercise (WL+EX) vs. exercise alone (EX). Participants will be randomized at Northwestern, Tulane University, and University of Minnesota. Our primary outcome is change in six-minute walk distance at 12-month follow-up. Secondary outcomes are change in 6-minute walk distance at 6-month follow-up and change in exercise adherence, physical activity, patient-reported walking ability (measured by the Walking Impairment Questionnaire (WIQ) distance score), and mobility (measured by the Patient-Reported Outcomes Measurement Information System \[PROMIS\] mobility questionnaire) at 12-month follow-up. Tertiary outcomes are perceived exertional effort (measured by the Borg scale at the end of the 6-minute walk at 12-month follow-up), and diet quality. Exploratory outcomes consist of change in the short physical performance battery (SPPB), the WIQ stair climbing and walking speed scores, and calf muscle biopsy measures at 12-month follow-up. Study investigators will perform calf muscle biopsies in 50 participants to compare changes in mitochondrial biogenesis and activity, capillary density, and inflammation between WL+EX vs. EX.

Community-based Exercise Following Revascularization for PAD

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.

Rotational Atherectomy and Drug-Coated Balloon Angioplasty With Embolic Protection for Superficial Femoral Artery Occlusions

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.

Improve PAD PERformance With METformin

The PERMET trial will determine whether metformin daily for six months improves six-minute walk performance in individuals with peripheral artery disease compared to placebo.

Vascular Regenerative Cell Exhaustion in Adults With Peripheral Artery Disease (PAD-VRCE)

PAD-VRCE is an observational, cross-sectional, two arm study aimed at determining if the presence of peripheral artery disease (PAD) can influence the number of circulating regenerative cells in blood. From peripheral blood samples, circulating progenitor cell content will be assessed via flow cytometry and compared between individuals with PAD and individuals without PAD. Ultimately, this study plans to evaluate the relationship between PAD, vascular regenerative cell exhaustion and overall cardiovascular health.

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

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.

Observational GORE® VIABAHN® Endoprosthesis With PROPATEN Bioactive Surface Global Registry

Collect real-world post-market clinical follow-up data on patients treated with the GORE® VIABAHN® Endoprosthesis with PROPATEN Bioactive Surface (VSX)

IV-X Medical First-in-Human Peripheral Intravascular Lithotripsy Study for PAD

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).

Leg Heat Therapy in Peripheral Artery Disease

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).

Women's Health Initiative Strong and Healthy Study

The WHISH trial applies state-of-the science behavioral principles and currently available technologies to deliver a physical activity intervention without face-to-face contact to \~25,000 older U.S. women expected to consent. It includes the National Institute of Aging (NIA) Go4Life® Exercise \& Physical Activity materials 3 and WHISH developed targeted materials based on Go4Life® to provide inspirational tips and recommendations about how to achieve nationally recommended levels of PA and overcome barriers to exercise, with a means for self-monitoring and setting personal goals. The intervention builds upon evidence-based behavioral science principles and intervention components that have proven to be effective in increasing PA in older women, with innovative adaptive approaches to tailoring the delivery to meet individual (personal) needs.

Response to Exercise and Nitric Oxide in PAD

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.

Prevalence of Obstructive Sleep Apnea in Patients With Peripheral Arterial Occlusive Disease

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.

The Value of Screening for HPR in Patients Undergoing Lower Extremity Arterial Endovascular Interventions

This is a randomized controlled trial designed to evaluate the role of screening for and intervening on patients with high on treatment platelet reactivity undergoing lower extremity arterial endovascular interventions.

Home-based Exercise Therapy in Patients With Moderate to Severe Peripheral Artery Disease

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.

Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease

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.

Randomized Controlled Trial of Alert-Based Computerized Decision Support for Patients With Peripheral Artery Disease Not Prescribed Lipid-Lowering Therapy

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.

Predictive Value of Systolic Rise Time of the Plantar Arch on the Risk of Major Adverse Limb Events (MALE) and Major Adverse Cardiovascular Events (MACE) in Peripheral Artery Disease (PAD) at Critical Ischaemia Stage

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 THOR IDE Study

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

Far Red Light to Improve Functioning in PAD

The LIGHT PAD Trial is a Phase II multi-centered randomized clinical trial to collect preliminary data to test whether daily far red light treatment of the lower extremities in people with PAD improves six-minute walk distance, lower extremity perfusion, and ischemia-related damage in gastrocnemius muscle at four-month follow-up, compared to a sham control. Participants will complete 10 minutes of twice daily home treatment with either far red light or a sham light for four months.

Chronical Illness-related Limitations of the Ability to Cope With Rising Temperatures, Third Wave

The CLIMATE-III Observational Study examines to what extent chronically ill patients experience adverse health effects because of heat and whether the patients' specific health behavior, somatosensory amplification, risk and benefit perception, self-efficacy, health literacy, and the degree of urbanisation of the patients' administration district are associated with these effects. Study participants from Germany and Italy will be included in the sample.