Neuromuscular Fatigue During Exercise in COPD-HF Overlap

Study Overview
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Brief Summary
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Rationale. Chronic obstructive pulmonary disease (COPD) and heart failure (HF) coexist in approximately one third of patients presenting with one of these conditions. From a clinical standpoint, impaired tissue oxygen (O2) delivery stands as a common pathological mechanism of these cardiorespiratory diseases. Recent evidence suggest that muscle and cerebral blood flow and oxygenation are further impaired during exercise in patients with COPD-HF overlap compared to isolated diseases. However, it remains unknown whether impaired O2 delivery is associated with exaggerated manifestations of peripheral and central fatigue in COPD-HF overlap. In addition, improving cardiopulmonary interactions through non invasive positive pressure ventilation or through the addition of a hyperoxic gas mixture during exercise have been associated with enhanced cerebral and muscle O2 delivery and oxygenation in patients with COPD or HF. It is, therefore, conceivable that improved O2 delivery to these structures have beneficial influence on exercise capacity in patients with COPD-HF overlap due to less peripheral and central fatigue. Aims. To investigate the influence of impaired O2 delivery during exercise, and its alleviation with different interventions (non invasive positive pressure ventilation ± hyperoxia), on neuromuscular fatigue in patients with COPD-HF.

Official Title
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Impaired Tissue Oxygen Delivery in Patients With Coexistent COPD-heart Failure: What Consequences on Neuromuscular Fatigue During Exercise?

Conditions
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Pulmonary Disease, Chronic Obstructive, Heart Failure

Intervention / Treatment
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* Other: Medical air
* Other: Non-invasive ventilation + Medical air
* Other: Non-invasive ventilation + Hyperoxia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; COPD: moderate-to-severe airflow obstruction (forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio <0.70; 30% ≤ post-bronchodilator FEV1 <80% predicted); HF: reduced left ventricular ejection fraction (<50%, for COPD-HF patients only); HF: New York Heart Association Functional Classification I to III (for COPD-HF patients only); Clinical stability for both diseases (COPD and/or HF) and no recent (within 3 months) exacerbation requiring a change in medications; Patient benefiting from health care coverage; Patient able to provide written informed consent. Exclusion Criteria: Inability to perform cycle ergometry; Medical device incompatible with magnetic stimulation; Counter-indication to perform exercise test; Patient refusing to sign written informed consent; Patient not benefiting from health care coverage; Patient exceeding the annual ceiling of authorized compensation received following participation to a clinical trial; Patient deprived of freedom by judicial or administrative decision; Patient subject to a measure of legal protection (safeguard of justice, guardianship, curatorship), who cannot be included in clinical trials; Pregnant or nursing woman.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 parralel study groups: patients with COPD (N=20); patients with COPD-HF overlap (N=20) Between-group comparison (COPD vs COPD-HF) under medical air Only patients with COPD-HF overlap exposed to interventions (non-invasive ventilation + medical air; non-invasive ventilation + hyperoxia)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Patients with COPD<br>Patients with COPD will only exercise under medical air (for between-group comparison: COPD vs COPD-HF) | Other: Medical air<br>* Exercise under medical air, both arms exposed.<br>|
| Experimental: Patients with COPD-HF overlap<br>Patients with COPD-HF overlap will first exercise under medical air (for between-group comparison: COPD vs COPD-HF); Patients with COPD-HF overlap will then exercise under interventions (randomized order: non-invasive ventilation + medical air; non-invasive ventilation + hyperoxia, for within-group comparison: medical air vs intervention trials) | Other: Medical air<br>* Exercise under medical air, both arms exposed.<br>Other: Non-invasive ventilation + Medical air<br>* Exercise under non-invasive ventilation, only experimental arm exposed.<br>Other: Non-invasive ventilation + Hyperoxia<br>* Exercise under non-invasive ventilation + hyperoxia, only experimental arm exposed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle fatigue | Muscle fatigue assessed by magnetic stimulation of the femoral nerve | Muscle fatigue assessed immediately after exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trials in COPD-HF) comparisons | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exertional symptoms | Symptoms of dyspnea, leg discomfort, and fatigue | Symptoms during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trials in COPD-HF) comparisons | 
| Tissue oxygenation | Prefrontal and quadriceps oxygenation (near-infrared spectroscopy) | Tissue oxygenation during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trials in COPD-HF) comparisons | 
| Cerebral blood flow | Middle cerebral artery blood flow velocity (transcranial Doppler ultrasonography) | Cerebral blood flow during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trials in COPD-HF) comparisons | 
| Cardiac output | Cardiac output (signal-morphology impedance cardiography) | Cardiac output during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trials in COPD-HF) comparisons | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise Tolerance, Hypoxia, Brain, Muscle Fatigue, Oxygen, Spectroscopy, Near-Infrared, Ultrasonography, Doppler, Transcranial