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

Peripheral Arterial Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06389149
• Other study ID #: 0165-24-FB
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2024
• Est. completion date: August 2025

Study information

• Verified date: May 2024
• Source: University of Nebraska
• Contact: Song-Young Park, PhD
• Phone: 402-554-3374
• Email: song-youngpark[@]unomaha.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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. To be eligible for this study, those with PAD must be between the ages of 50-85 years, women must be postmenopausal, must have a history of exercise-limiting claudication, have an ankle brachial index (ABI) 0.9. 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. There will be no follow-up.

Description:

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-min every 10-min. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

At entry into the study, PAD subjects must:

1. be able to provide written informed consent

2. be between the ages of 50-85

3. be diagnosed as Fontaine stage II-III

4. women must be postmenopausal (cessation of menses for > 24 mo)

5. demonstrate a history of exercise-induced claudication

6. must not have ulcers, gangrene, or necrosis of the foot (Fontaine stage IV PAD)

7. not have kidney disease or type II diabetes mellitus

At entry into the study, age-matched control subjects must:

1. be able to provide written informed consent

2. be between the ages of 50-85

3. have no evidence of peripheral occlusive disease (ankle-brachial index > 0.90)

4. women must be postmenopausal (cessation of menses for > 24 mo)

5. not have kidney disease or type II diabetes mellitus

Exclusion Criteria:

Potential subjects with PAD will be deemed ineligible if they:

1. have pain at rest and/or tissue loss due to PAD (Fontaine stage IV PAD)

2. have an acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma

3. have limited walking capacity due to conditions other than PAD

4. have not had a physical exam to assess exercise limitations in the past year.

5. are currently pregnant or nursing

6. currently have kidney disease or type II diabetes mellitus

Potential age-matched control subjects will be deemed ineligible if they:

1. have a positive diagnosis of PAD

2. have any exercise limitations as determined by a doctor at their last physical exam (at or before 1 year prior to the study)

3. have not had a physical exam to assess exercise limitations in the past year.

4. have limited walking capacity from musculoskeletal injury

5. are currently pregnant or nursing

6. currently have kidney disease or type II diabetes mellitus

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Artery Disease
• Peripheral Artery Occlusive Disease
• Peripheral Vascular Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

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

Locations

Country	Name	City	State
United States	University of Nebraska - Omaha	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

United States, 

References & Publications (54)

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* Note: There are 54 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Macrovascular Endothelial Function	Macrovascular endothelial function will be measured non-invasively using the flow-mediated dilation (FMD) technique in the brachial and popliteal arteries using a Doppler ultrasound. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.
Primary	Microvascular Vasodilatory Capacity	Microvascular vasodilatory capacity will be measured as the near-infrared spectroscopy (NIRS) reoxygenation rate in the medial gastrocnemius after an arterial occlusion. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.
Primary	Femoral and Popliteal Artery Blood Flow	Femoral and popliteal artery blood flow will be measured in both legs using Doppler ultrasound. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.
Primary	Walking capacity	Physical walking capacity will be measured during the Gardner treadmill protocol. Participants will walk on a treadmill at 2.0 miles per hour (mph). Grade will began at zero and will be increased by two percent every two minutes. Participants unable to walk at least 2.0 mph begin walking at 0.5 mph and their speed is increased by 0.50 mph every two minutes until the participant reaches 2.0 mph. After reaching 2.0 mph, treadmill grade is increased by two percent every two minutes. Participants are asked to continue walking without stopping until they cannot continue because of leg symptoms, exhaustion, or other symptoms. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.
Primary	Autonomic Function	Autonomic nervous system function will be measured non-invasively using heart rate variability via the head-up tilt test. Raw R-R interval data will be converted to time frequency domain with the wavelet transform across the frequency intervals 0.04-0.15 Hz (low-frequency, (LF)) and 0.15-0.4 Hz (high-frequency, HF). Units for both will be expressed as ms^2. Final outcome measure will be the ratio of LF/HF, which is a unitless ratio to indicate sympathetic-to-parasympathetic nervous system function. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.
Primary	Autonomic Activity	Autonomic activity will be measured with a 3-lead ECG system (7700 Series, IvyBiomedical Systems Inc., Branford, CT) and will be used to continuously collect heart electrical activity during prolonged sitting with LEAP therapy, and prolonged sitting without LEAP therapy. Raw R-R interval data will be converted to time frequency domain with the wavelet transform across the frequency intervals 0.04-0.15 Hz (low-frequency, (LF)) and 0.15-0.4 Hz (high-frequency, HF). Units for both will be expressed as ms^2. Final outcome measure will be the ratio of LF/HF, which is a unitless ratio to indicate sympathetic-to-parasympathetic nervous system function.	Day 1: during the condition. Day 7: during the condition
Primary	Arterial Stiffness	Peripheral and central arterial stiffness will be assessed non-invasively using pulse-wave velocity via the applanation tonometry technique. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.
Primary	Muscle Oxygenation	A near-infrared spectroscopy (NIRS) sensor will be adhered on the skin above the belly of the medial gastrocnemius muscle to non-invasively assess muscle oxygenation during the entire prolonged sitting bout with LEAP therapy, and the entire prolonged sitting bout without LEAP therapy.	Day 1: during the condition. Day 7: during the condition
Primary	Peripheral blood mononuclear cell mitochondrial function	Participants will have blood drawn from an antecubital vein, which will be used to isolate peripheral blood mononuclear cells (PBMCs) and assess their mitochondrial function. These measures will be performed before and after 2.5 hours of prolonged sitting with LEAP therapy, and before and after 2.5 hours of prolonged sitting without LEAP therapy.	Day 1: before and after condition. Day 7: before and after condition.