Hypoxic Exercise in Lower Extremity Artery Disease

Study Overview
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Brief Summary
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The aim of this randomized controlled trial is to: Phase I: To explore, in a first pilot phase, the adequate combination of hypoxia severity and exercise intensity in patients with symptomatic lower extremity artery disease (LEAD). Acute walking performances and physiological responses (vascular and muscular) to a normobaric hypoxic exercise performed will be assessed at two different altitudes (1500 m and 2500 m).

Detailed Description
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The results of this first phase will then be used to determine the optimal hypoxic level for the exercise training program which will be assessed during the Phase II.

Official Title
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Exercise Training Under Hypoxic Conditions in Lower Extremity Artery Disease

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Other: Exercise in hypoxia 1500m
* Other: Exercise in hypoxia 2500m
* Other: Exercise in normoxia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic LEAD (Fontaine stage ≥ IIa) ABI ≤ 0.9 TBI ≤ 0.6 if incompressible arteries (diabetes and renal insufficiency) Signed written informed consent form Exclusion Criteria: Neurological and neuromuscular disorders which can limit balance and walking Any history of altitude-related sickness Any health risks (assessed during clinical history) linked to hypoxia exposure Acclimatization or exposure to hypoxia of more than 2000 m for more than 48 h during a period of 6 months before the study Medication required for the treatment of migraines, claustrophobia that may interfere with the interpretation of the results Obstructive sleep apnea (> 25 Apnea-Hypopnea Index) Prior leg/foot amputation Pregnant women Cardiac contraindication to exercise

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise in hypoxia 1500m<br>During this visit, subjects will perform a 6-min treadmill exercise wearing an oronasal mask connected (through a hose) with a three-way valve to an altitude simulation device (Altitrainer; SMTech, Nyon, Switzerland). The ambient air will be mixed with nitrogen and inspired oxygen fraction will be reduced to 16%. | Other: Exercise in hypoxia 1500m<br>* Subjects will perform a 6-min treadmill exercise wearing an oronasal mask connected (through a hose) with a three-way valve to an altitude simulation device (Altitrainer; SMTech, Nyon, Switzerland). The ambient air will be mixed with nitrogen and inspired oxygen fraction will be reduced to 16%. The first 3 min will be performed at 70% of the mean speed calculated during a previous visit, and the last 3 min at an intensity between 12-14 on the Borg's scale.<br>|
| Experimental: Exercise in hypoxia 2500m<br>During this visit, subjects will perform a 6-min treadmill exercise wearing an oronasal mask connected (through a hose) with a three-way valve to an altitude simulation device (Altitrainer; SMTech, Nyon, Switzerland). The ambient air will be mixed with nitrogen and inspired oxygen fraction will be reduced to 14%. | Other: Exercise in hypoxia 2500m<br>* Subjects will perform a 6-min treadmill exercise wearing an oronasal mask connected (through a hose) with a three-way valve to an altitude simulation device (Altitrainer; SMTech, Nyon, Switzerland). The ambient air will be mixed with nitrogen and inspired oxygen fraction will be reduced to 14%. The first 3 min will be performed at 70% of the mean speed calculated during a previous visit, and the last 3 min at an intensity between 12-14 on the Borg's scale.<br>|
| Placebo Comparator: Exercise in normoxia<br>During this visit, subjects will perform a 6-min treadmill exercise wearing an oronasal mask connected (through a hose) with a three-way valve to an altitude simulation device (Altitrainer; SMTech, Nyon, Switzerland). For the exercise performed in normoxia conditions, subjects will breathe room air. | Other: Exercise in normoxia<br>* Subjects will perform a 6-min treadmill exercise wearing an oronasal mask connected (through a hose) with a three-way valve to an altitude simulation device (Altitrainer; SMTech, Nyon, Switzerland). For the exercise performed in normoxia conditions, subjects will breathe room air. The first 3 min will be performed at 70% of the mean speed calculated during a previous visit, and the last 3 min at an intensity between 12-14 on the Borg's scale.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking performance | Total walking distance (in meters) during the 6 min treadmill test | After each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Pain free walking time | Pain free walking time during the 6 min treadmill test | After each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Muscle oxygenation during exercise | Muscle oxygenation during the 6 min treadmill test (assessed by near-infrared spectroscopy) | After each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Pulse wave velocity | Pulse wave velocity before and after the 6 min treadmill test | Before and after each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Flow-mediated dilation | Flow-mediated dilation before and after the 6 min treadmill test | Before and after each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Pulse oxygen saturation | Pulse oxygen saturation during the 6 min treadmill test | After each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankle-brachial index | Ankle-brachial index before and after the 6 min treadmill test | Before and after each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Toe-brachial index | Toe-brachial index before and after the 6 min treadmill test | Before and after each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Rate of perceived exertion | Rate of perceived exertion (RPE) will be assessed using Borg's scale. RPE is a widely used and reliable indicator to monitor and guide exercise intensity. The scale allows individuals to subjectively rate their level of exertion during 6 min treadmill test. Patients will classify their RPE between 6 (light) and 20 (maximal). | After each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 
| Leg pain | Leg pain during exercise will be measured with a 10-points (0: no pain and 10: worst imaginable pain) visual analogic scale (VAS). | After each 6 min treadmill test performed under hypoxic condition (1500 and 2500 m) and under normoxic condition (i.e., average of 3 weeks; one condition per week) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, cardiovascular, normobaric hypoxia