Dynamic Respiratory Muscle Function in Late-Onset Pompe Disease

Study Overview
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Brief Summary
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This study intends to evaluate dynamic respiratory motor performance as a valuable measure of pulmonary function in adults with late-onset Pompe disease. The investigators will adopt a strategy that includes comprehensive evaluations of respiratory volume, flow, and timing parameters during resting and loaded breathing. These evaluations will then be associated to the standard clinical measure of maximal inspiratory pressure, the static inspiratory muscle function, as well as magnetic resonance imaging of thoracic expansion and diaphragmatic descent at rest and with exertion. Outcomes in participants with late-onset Pompe disease will be contrasted to the function of age- and gender-matched control subjects. This approach will enable the investigators to evaluate the relationship between dynamic diaphragmatic function and respiratory motor function.

Detailed Description
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The following tests will be completed over a two-day period: Respiratory pressure tests, breathing test, magnetic resonance imaging and magnetic resonance spectroscopy (MRI and MRS).

Official Title
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Dynamic Respiratory Muscle Function in Late-Onset Pompe Disease

Conditions
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Pompe Disease

Intervention / Treatment
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* Other: Thoracic MRI
* Other: Spirometry
* Other: Inspiratory Load Compensation
* Other: Maximal Inspiratory Pressure
* Other: Resting Breathing Pattern
* Other: Respiratory Muscle Endurance Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Pompe disease OR Be an age and gender-matched unaffected control subject Exclusion Criteria: Pre-existing obstructive lung disease or asthma Forced vital capacity (FVC) <30% or >80% of age/gender predicted values Inability to travel to the study site Requirement for positive pressure ventilator support when awake and upright Participation in longitudinal studies that may independently alter lung function Presence of any other chronic medical condition that, in the opinion of the investigator, would make the subject unsuitable for the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pompe subjects<br>These subjects will receive a thoracic MRI, spirometry, inspiratory load compensation, maximal inspiratory pressure, resting breathing pattern, respiratory muscle endurance test. | Other: Thoracic MRI<br>* Imaging of the diaphragm will be completed during resting breathing, and then during a maximal voluntary ventilation maneuver.<br>Other: Spirometry<br>* Upright forced vital capacity (FVC)<br>Other: Inspiratory Load Compensation<br>* A spring-loaded pressure device will resist inspiration. The patient must generate the threshold inspiratory pressure to receive airflow. The changes in breathing timing, flow and volume will be recorded.<br>Other: Maximal Inspiratory Pressure<br>* Measure the maximal airflow on inhalation<br>* Other names: MIP;Other: Resting Breathing Pattern<br>* The breathing pattern will be assessed when the subject is seated and in a relaxed state.<br>Other: Respiratory Muscle Endurance Test<br>* Evaluates the time limit that a participant can maintain ventilation while breathing with a submaximal inspiratory threshold load.<br>|
| Control subjects<br>These subjects will receive a thoracic MRI, spirometry, inspiratory load compensation, maximal inspiratory pressure, resting breathing pattern, respiratory muscle endurance test. | Other: Thoracic MRI<br>* Imaging of the diaphragm will be completed during resting breathing, and then during a maximal voluntary ventilation maneuver.<br>Other: Spirometry<br>* Upright forced vital capacity (FVC)<br>Other: Inspiratory Load Compensation<br>* A spring-loaded pressure device will resist inspiration. The patient must generate the threshold inspiratory pressure to receive airflow. The changes in breathing timing, flow and volume will be recorded.<br>Other: Maximal Inspiratory Pressure<br>* Measure the maximal airflow on inhalation<br>* Other names: MIP;Other: Resting Breathing Pattern<br>* The breathing pattern will be assessed when the subject is seated and in a relaxed state.<br>Other: Respiratory Muscle Endurance Test<br>* Evaluates the time limit that a participant can maintain ventilation while breathing with a submaximal inspiratory threshold load.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inspiratory load compensation | Peak inspiratory flow, inspiratory volume, and duty cycle of loaded breaths will be measured | Day 1 | 
| Respiratory muscle endurance task | Time and load associated with endurance task failure will be measured. | Day 2 | 
| Inspiratory load Compensation | Peak inspiratory flow, inspiratory volume, and duty cycle of loaded breaths will be measured | Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thoracic MRI | Chest wall and diaphragmatic motions will be measured in three planes with dynamic magnetic resonance imaging (MRI). The change in diaphragm excursion between full inspiration and full expiration will be measured in the frontal plane, and change in the area of the right and left sides of the chest cavity will be measured in the sagittal plane. Diaphragm and chest excursion will be recorded dynamically during 30-second periods of resting breathing and deep breathing. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spirometry, respiratory test, respiratory muscle endurance