Muscle Metabolism and Oxygenation During Localized Fatigue-exercise in COPD

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether a localized exercise, in which cardiorespiratory demand is reduced, will result in greater limb muscle fatigue in patients with COPD as a consequence of muscle oxygenation and muscle metabolism disturbances.

Official Title
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Muscle Oxygenation and Metabolism in Response to a Localized Fatigue-inducing Exercise in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Other: Fatiguing exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD (FEV1/FVC < 0.70 and FEV1 < 0.80 predicted Healthy subjects: no evidence of airways obstruction (FEV1/FVC > 0.70 and FEV1 > 0.80 predicted) Smoking history > 15 pack-years Exclusion Criteria: Chronic hypoxemia and/or hypercapnia (PaO2 < 60 mmHg or SpO2 < 88% at rest and/or PaCO2 > 45 mmHg) Recent exacerbation (< 3 months) Recent cancer (< 3 years) Diabetes Myopathy, neuromuscular or articular disease Unstable cardiac disease Absolute contraindications to exercise testing Regular physical activity or exercise training program in the last 2 months Physical activity score > 9 in the Voorips questionnaire Thigh skinfold thickness > 15 mm BMI > 30

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxygen<br> | Other: Fatiguing exercise<br>* All participants (patients and healthy subjects) will perform the exercise both under normoxic (FiO2 = 0.21) and hyperoxic conditions (FiO2 = 100%)<br>|
| Sham Comparator: Room air<br> | Other: Fatiguing exercise<br>* All participants (patients and healthy subjects) will perform the exercise both under normoxic (FiO2 = 0.21) and hyperoxic conditions (FiO2 = 100%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle deoxygenation | Changes of deoxyhemoglobin/myoglobin concentrations measured by near-infrared spectroscopy of vastus lateralis muscle. | 45 seconds post-exercise (knee-extension repetitions) | 
| Muscle metabolism | Changes in glycolytic and oxidative metabolism pathway markers, energy substrates (glycogen and glucose), end-products of glycolysis (pyruvate, and lactate), intermediate markers of glycolysis and high-energy phosphate compounds obtained from muscle biopsies | 45 seconds post-exercise (knee extension repetitions) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory response | Minute ventilation will be monitored during the fatigue-inducing exercise and it will be compared between subjects and conditions (FiO2 = 21% vs. FiO2 = 100%) | Baseline, beginning and end of each serie of knee extensions (fatiguing exercise) | 
| Quadriceps muscle fatigue | Quadriceps muscle fatigue will be determined by loss of quadriceps strength measured by magnetic stimulation after the fatigue-inducing exercise. Surface electromyography will also be measured to characterize muscle fatigue. | baseline, 15 min and 40 min after the fatigue-inducing exercise | 
| total muscle work | Total muscle work performed during fatigue-inducing exercise that will be composed by subsequent isokinetic knee-extensions repetitions at 40% of maximal peak torque | end of fatiguing exercise | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Disease, Chronic Obstructive, Muscle fatigue, Energy metabolism, Muscle oxygenation