Assessment of Cardiopulmonary Function in Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This study seeks to develop and validate non-invasive assessments of cardiac and respiratory muscles with magnetic resonance imaging (MRI) to better predict the natural disease progression of Duchenne muscular dystrophy (DMD) in affected individuals over time, as well as determine whether peripheral skeletal muscle dysfunction can predict cardiopulmonary dysfunction. The central hypothesis is that non-invasive MRI measures of the heart, muscle, and peripheral skeletal muscles can sensitively predict future cardiopulmonary decline.

Detailed Description
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Magnetic Resonance Imaging (MRI) of the heart and breathing muscles, special breathing tests (called pulmonary function testing), special exercise tests (using a stationary bike), and possibly an echocardiogram (ultrasound of the heart, commonly known as an echo) will be completed up to 4 times per year for up to 4 years. Most participants will complete testing once or twice each year; however, some participants will be asked to repeat some of the tests twice during each visit.

Official Title
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Assessment of Cardiopulmonary Function in Duchenne Muscular Dystrophy

Conditions
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Muscular Dystrophy, Duchenne

Intervention / Treatment
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* Other: Magnetic Resonance Imaging (MRI)
* Other: Pulmonary Function Testing (PFT)
* Other: Metabolic Exercise Testing using stationary bicycle
* Other: Echocardiogram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 5-15 years old at the time of enrollment Diagnosed with DMD (as defined by parent project) Written parental informed consent (and assent where appropriate) before any study procedures take place Exclusion Criteria: Contraindication to an MRI examination Presence of a secondary condition that impacts muscle function or metabolism, that leads to developmental delay or impaired motor control, or that is not stable Participant is unable to comply with study requirements Congenital structural abnormality of the heart, repaired or unrepaired Clinically contraindicated participation

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals with DMD<br>Magnetic Resonance Imaging is a non-invasive method to determine ventricular size, volumes, mass, and ejection fraction. Pulmonary Function testing (PFT) are a series of non-invasive breathing tests that characterize respiratory muscle function, as well as lung compliance and physiology. Metabolic exercise testing using stationary bicycle (exercise capacity and MVO2) evaluates global cardiopulmonary functional status. Echocardiogram with multiple-echo Dixon method helps to assess cross-sectional and longitudinal variations in myocardial structure. | Other: Magnetic Resonance Imaging (MRI)<br>* It is a non-invasive method to determine ventricular size, volumes, mass, and ejection fraction.<br>Other: Pulmonary Function Testing (PFT)<br>* It is non-invasive breathing tests that characterize respiratory muscle function, as well as lung compliance and physiology.<br>Other: Metabolic Exercise Testing using stationary bicycle<br>* Metabolic exercise testing, including assessment of exercise capacity and MVO2, evaluates global cardiopulmonary functional status. This is performed with the use of a stationary bicycle.<br>Other: Echocardiogram<br>* The echocardiogram performed with the multiple-echo Dixon method helps to assess participants cross-sectionally and longitudinally for variations and changes in myocardial structure.<br>* Other names: Multiple-echo Dixon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnetic Resonance (MRI) T2 and Magnetic Resonance Spectroscopy (MRS) | The MRI T2 and MRS will be used as a noninvasive marker of myocardial damage/inflammation of participants of this study as an early detection for DMD. | up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Function Testing (PFT) | Non-invasive breathing tests that characterize respiratory muscle function, as well as lung compliance and physiology. | up to 4 years | 
| Metabolic Exercise Testing (exercise capacity and MVO2) | With the use of metabolic exercise testing, the aim is to correlate changes in cardiopulmonary function with decline in peripheral skeletal muscle function in individuals with DMD. Metabolic exercise testing includes measuring exercise capacity and maximum oxygen consumption (MVO2). | up to 4 years | 
| Multiple-echo Dixon | The echocardiogram performed with the multiple-echo Dixon method helps to assess participants cross-sectionally and longitudinally for variations and changes in myocardial structure. This method and MRS will also be used for fat fraction determination. | up to 4 years |