Validating Cardiac MRI Biomarkers and Genotype-Phenotype Correlations for DMD

Study Overview
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Brief Summary
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This study will collect MRI from healthy volunteer boys and boys with Duchenne Muscular Dystrophy (DMD) to help researchers identify and validate cardiac MRI biomarkers to better understand the health of the heart and changes in heart health over time in boys with DMD. Currently, there is a lack of sufficiently well characterized cardiac MRI biomarkers that can serve as endpoints for detecting on-target and/or off-target cardiac effects during clinical drug trials for boys with DMD. Consequently, the first objective is to identify and characterize several cardiac MRI biomarkers for boys with DMD.

Detailed Description
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The second objective is to use their well-characterized cardiac MRI biomarkers and define their sensitivity for detecting early cardiac involvement. The final objective is to use these validated cardiac MRI biomarkers to better understand the genotype-phenotype correlation in boys with DMD, which to date remain tenuous. The investigators propose a pilot study to explore cardiac genotype-phenotype correlations in boys with DMD and outlier phenotypes using approaches they have pioneered for skeletal muscle.

Official Title
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Validating Cardiac MRI Biomarkers and Genotype-Phenotype Correlations for Duchenne Muscular Dystrophy (DMD)

Conditions
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Muscular Dystrophy, Duchenne

Intervention / Treatment
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* Other: Cardiac MRI with contrast
* Other: Cardiac MRI without contrast
* Other: Blood Test
* Other: Heart Rate
* Other: Pulmonary Function Test
* Other: Genetic Testing
* Other: Repeat MRI scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy boys or pediatric patients with DMD age 7 to 21 Able & willing to complete an approximately 75-minute (or less) MRI exam without sedation or mechanical ventilation Drug regimen (if applicable) stable for at least 3 months prior to participation Exclusion Criteria: Renal insufficiency (GFR<40 mL/min/m2) Non-MRI compatible implants (e.g. neurostimulator, pacemaker, implanted cardioverter defibrillator) Claustrophobia that prevents an MRI exam Known allergy to MRI contrast agents Serum potassium level of >5.0 mmol/L Signs and symptoms of heart failure

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1a<br>Group 1a comprises healthy volunteers who will complete a Cardiac MRI without contrast. A subset of healthy volunteers will have a repeat MRI at Children's Hospital of Orange County. | Other: Cardiac MRI without contrast<br>* Cardiac MRI<br>Other: Repeat MRI scan<br>* Repeat MRI scan<br>|
| Experimental: Group 1b<br>Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County. | Other: Cardiac MRI with contrast<br>* Cardiac MRI<br>Other: Blood Test<br>* Hematocrit, Creatinine, Troponin, BNP<br>Other: Heart Rate<br>* Holter Monitor<br>Other: Pulmonary Function Test<br>* Pulmonary Function Test<br>Other: Genetic Testing<br>* Genetic Testing<br>Other: Repeat MRI scan<br>* Repeat MRI scan<br>|
| Experimental: Group 2<br>Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months. | Other: Cardiac MRI with contrast<br>* Cardiac MRI<br>Other: Blood Test<br>* Hematocrit, Creatinine, Troponin, BNP<br>Other: Heart Rate<br>* Holter Monitor<br>Other: Pulmonary Function Test<br>* Pulmonary Function Test<br>Other: Genetic Testing<br>* Genetic Testing<br>Other: Repeat MRI scan<br>* Repeat MRI scan<br>|
| Experimental: Group 3<br>Group 3 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a genetic testing. | Other: Cardiac MRI with contrast<br>* Cardiac MRI<br>Other: Blood Test<br>* Hematocrit, Creatinine, Troponin, BNP<br>Other: Heart Rate<br>* Holter Monitor<br>Other: Pulmonary Function Test<br>* Pulmonary Function Test<br>Other: Genetic Testing<br>* Genetic Testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Tissue Characterization | Focal and diffuse fibrosis, intra myocardial fat, edema plus water mobility | 6 months | 
| Myocardial Functional Characterization | Strain imaging and rotational mechanics | 6 months | 
| Genomic Analysis | Proposing mechanisms of cardiac dysfunction or protective phenotypes using genomic analysis | 4 years |