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

NCT06389149 | Recruiting

• 1 other identifier: 0165-24-FB
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Peripheral Arterial Disease; Peripheral Vascular Disease; Peripheral Artery Occlusive Disease; Peripheral Artery Disease

Outcome Measures

Primary Outcomes (9)

• 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.

• 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.

• 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.

• 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.

• 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.

• 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

• 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.

• 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

• 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.

Study Arms (4)

Control: LEAP therapy, then no LEAP therapy

EXPERIMENTAL

Participants will perform a bout of 2.5 hours of prolonged sitting with LEAP therapy. After a minimum period of 7 days, they will then perform a bout of 2.5 hours of prolonged sitting without LEAP therapy.

Other: LEAP therapy; Other: no LEAP therapy

Control: No LEAP therapy, then LEAP therapy

EXPERIMENTAL

Participants will perform a bout of 2.5 hours of prolonged sitting without LEAP therapy. After a minimum period of 7 days, they will then perform a bout of 2.5 hours of prolonged sitting with LEAP therapy.

Other: LEAP therapy; Other: no LEAP therapy

PAD: LEAP therapy, then no LEAP therapy

EXPERIMENTAL

Participants with peripheral artery disease will perform a bout of 2.5 hours of prolonged sitting with LEAP therapy. After a minimum period of 7 days, they will then perform a bout of 2.5 hours of prolonged sitting without LEAP therapy.

Other: LEAP therapy; Other: no LEAP therapy

PAD: No LEAP therapy, then LEAP therapy

EXPERIMENTAL

Participants with peripheral artery disease will perform a bout of 2.5 hours of prolonged sitting without LEAP therapy. After a minimum period of 7 days, they will then perform a bout of 2.5 hours of prolonged sitting with LEAP therapy.

Other: LEAP therapy; Other: no LEAP therapy

Interventions

LEAP therapy OTHER

Knee bending from 90°-180° at 1Hz for 1 minute every 10 minutes during 2.5 hours of prolonged sitting

Control: LEAP therapy, then no LEAP therapy; Control: No LEAP therapy, then LEAP therapy; PAD: LEAP therapy, then no LEAP therapy; PAD: No LEAP therapy, then LEAP therapy

no LEAP therapy OTHER

2.5 hours of uninterrupted prolonged sitting (no movement)

Control: LEAP therapy, then no LEAP therapy; Control: No LEAP therapy, then LEAP therapy; PAD: LEAP therapy, then no LEAP therapy; PAD: No LEAP therapy, then LEAP therapy

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska - Omaha

Omaha, Nebraska, 68182, United States

RECRUITING

Related Publications (54)

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MeSH Terms

Conditions

Peripheral Arterial Disease; Peripheral Vascular Diseases; Peripheral Arterial Occlusive Disease 1

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Song-Young Park, PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Song-Young Park, PhD

CONTACT

402-554-3374; song-youngpark@unomaha.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There will be a peripheral artery disease (PAD) group and an age-matched healthy control group. Within each of these groups will be a 1:1 randomized, crossover study design.

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: August 16, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)