Effects of Combined Aerobic and Resistance Training in Patients With Intermittent Claudication

Study Overview
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Brief Summary
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Exercise training improves walking capacity and regional perfusion in patients with Intermittent Claudication (IC). Endothelial Progenitor Cells (EPCs) and Endothelial Microparticles (EMPs) could play an important role in this process, promoting the healing of the diseased endothelium. The investigators are going to measure EPCs and EMPs in a group of patients with IC and in a control group of healthy individuals before a treadmill test and 2, 24, and 48 hours after the test. Subsequently, a group of IC patients will be randomly assigned to perform a 12-week home-based exercise training program. The investigators expect a significant increase of EMPs and EPCs after acute and chronic physical activity. We expect also a correlation between the increase of EMPs and EPCs and the improvement in walking capacity. Aim of the study is to demonstrate that acutely performed aerobic exercise could be able to promote the mobilization of EMPs and EPCs in patients with IC and that endothelial progenitor cells mobilization could play a pivotal role in exercise induced improvement of walking performance and endothelial function in subjects with IC.

Official Title
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Effects of Home-based Combined Aerobic and Resistance Training on Walking Capacity, Circulating Endothelial Progenitor Cells AND Endothelial Function in Patients With Intermittent Claudication

Conditions
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Peripheral Arterial Disease, Endothelial Dysfunction

Intervention / Treatment
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* Behavioral: combined aerobic and resistance physical activity
* Behavioral: sham exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: history of stable intermittent claudication (PAD, stage II Fontaine) resting ankle-brachial index (ABI) <0,9 and the presence of occlusion or significant stenosis at the color-Doppler duplex ultrasound scanning Exclusion Criteria: lower-limb ischemic rest pain or gangrene (Fontaine stages III and IV) inability to obtain the ABI value or to perform a walking test exercise tolerance limited by factors other than claudication (i.e., arrhythmias, cardiac symptoms or exaggerated blood pressure rise, severe obesity) end-stage liver or renal failure acute or chronic inflammatory conditions history of recent (<6 months) acute coronary syndrome, cerebrovascular event or inducible myocardial ischemia treatment with drugs known to affect walking capacity, including calcium-channel blockers, β-blockers and angiotensin-converting enzyme inhibitors.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy control<br>Voluntary subjects without peripheral arterial disease | |
| Sham Comparator: IC patients, no exercise<br>Patients with peripheral arterial disease stage II (intermittent claudication) on best medical treatment, given advices to perform regular aerobic activity | Behavioral: sham exercise<br>* general recommendation to perform regular aerobic physical activity<br>|
| Active Comparator: IC patients, exercise<br>Patients with peripheral arterial disease stage II (intermittent claudication) on best medical treatment, home-based combined physical exercise | Behavioral: combined aerobic and resistance physical activity<br>* Five training sessions weekly for 12 weeks are scheduled. Each session lasts 60 minutes divided into 45 minutes of aerobic workout and 15 minutes of circuit training. The aerobic workout consists of walking on a flat floor or on a slight uphill (maximum slope 3%): patients should walk until submaximal walking capacity (80% of their MWT) and rest as they would experience pain at the lower limbs; afterwards, they should start to walk again, once the pain was improved. Resistance training consists of calisthenics exercises focused on trunk and lower limbs muscles (bicycle, flutter kicks, squats, lunges, calf raises, wall sits and power press) with at least 3 repetitions for each exercise, interspersed by 30 seconds recovery. Duration of repetitions increases every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Microparticles (EMPs) | hematological parameter, cells particles released by activated endothelium, measured by cytofluorimetry | week 0 - week 12 | 
| Endothelial Progenitor Cells (EPCs) | hematological parameter, immature bone-marrow derived cells which repair the damaged endothelium, measured by cytofluorimetry | week 0 - week 12 | 
| Maximum Walking Time | functional parameter, maximum walking capacity for an individual with IC measured through a treadmill walking test | week 0 - week 12 | 
| Pain-free Walking Time | maximum walking capacity for an individual with IC without experiencing pain measured through a treadmill walking test | week 0 - week 12 | 
| Flow-mediated Dilation | ultrasonographic evaluation of endothelial function | week 0 - week 12 |