RELVAR Effects on Parasternal Muscle Activity, Diaphragm, and Ventilation in Severe COPD

Study Overview
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Brief Summary
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This study examines the effect of the ultra long acting beta agonist/corticosteroid bronchodilator combination fluticasone furoate/vilanterol trifenatate, on respiratory muscles and ventilation in adults with severe bronchitis or emphysema (COPD).

Detailed Description
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In adults with severe, minimally reversible bronchitis or emphysema (COPD), there is progressive hyperinflation of the lungs with associated flattening and inefficiency of the major respiratory muscle, the diaphragm. These changes limit physical activity and exercise, and provoke shortness of breath - dyspnea. These debilitating symptoms are often significantly lessened with ultra long acting combination bronchodilators, even in adults where the bronchodilator does not produce any measurable improvement in either airflow or lung hyperinflation. This symptomatic improvement in adults with severe, minimally reversible COPD may occur because of a direct benefit of the bronchodilator on respiratory muscles and ventilation. This study examines the effect of the ultra long acting bronchodilator fluticasone furoate/vilanterol trifenatate upon the upper anterior chest wall respiratory muscles (parasternals), the diaphragm, and breathing pattern.

Official Title
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RELVAR Effects on Parasternal Muscle Activity, Diaphragm, and Ventilation in Severe COPD

Conditions
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Copd

Intervention / Treatment
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* Procedure: Ventilation
* Procedure: Parasternal EMG
* Procedure: Phrenic magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ambulatory, stable severe COPD (GOLD Class III-IV) on long acting bronchodilator therapy compliant with use of prescribed medications fit for minor surgical procedure including intravenous sedation Exclusion Criteria: hypersensitivity to milk proteins hypersensitive to fluticasone furoate/vilanterol formulation angina or substantial cardiovascular risk exacerbation of COPD within the preceding 2 months significant non-respiratory system disease

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
Intervention Model: Single Group Assignment
Interventional Model Description: Study of RELVAR drug effect on respiratory physiology variables including breathing pattern, and EMG.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone vilanterol bronchodilator<br>Inhalation of fluticasone furoate/vilanterol trifenatate, 100 mcg/25 mcg combination, bronchodilator,using standard dry powder inhaler. Interventions include ventilation, parasternal EMG, and phrenic magnetic stimulation. | Procedure: Ventilation<br>* Measurements of ventilation with subjects seated, and breathing across a pneumotachygraph and pressure transducer to measure inspiratory airflow, during both resting and CO2 stimulated breathing.<br>Procedure: Parasternal EMG<br>* Recordings of electrical activity (EMG) from the parasternal intercostal muscle in the second intercostal space on the upper anterior chest wall adjacent to the sternum.<br>Procedure: Phrenic magnetic stimulation<br>* Bilateral maximal magnetic stimulation (Magstim) of the phrenic nerves.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minute ventilation change | Minute ventilation will be averaged and compared, before and then 2 hours after the bronchodilator inhalation. | 2 hours after fluticasone furoate/vilanterol bronchodilator inhalation. | 
| Parasternal EMG change | Change in moving averaged, EMG continuously recorded from the parasternal intercostal muscle. | 2 hours after fluticasone furoate/vilanterol bronchodilator inhalation. | 
| Pressure change with phrenic stimulation | Change in recorded mouth pressure during magnetic stimulation of the phrenic nerves. | 2 hours after fluticasone furoate/vilanterol bronchodilator inhalation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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respiratory muscle, bronchodilator