Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of DMD and BMD

Study Overview
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Brief Summary
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Longitudinal prospective observational study. This is a 24-month study with the possibility of extending the data time points. Initially baseline, then 12 and 24 months follow up studies will be completed.

Detailed Description
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Four cohorts are enrolled in this study. The target population is the cohort of genetically confirmed DMD/BMD female carriers (Cohort A). This cohort will consist of 150 DMD/BMD mothers who are somatic carriers of a mutation in the DMD gene. The data collected for this cohort will be compared to three control groups; Control Group B is a cohort of 50 DMD/BMD mothers who are NOT somatic carriers, Control Group C is a cohort of 50 age-matched healthy controls and Control Group D is a cohort of 25 genetically confirmed carriers who do not have an affected child. The inclusion of a Control Group B allows for a comparison to a group of mothers that share the emotional and cognitive burden of caring for an affected male without having the physical or cognitive risks of being a female carrier. The Control Group C offers robust data from an age-matched healthy cohort for purposes of comparison. Control Group D allows for comparison to a group of women that have the same physical or cognitive risks as the Cohort A female carriers, but do not have the same burden of care giving.

Official Title
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Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)

Conditions
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Duchenne Muscular Dystrophy, Becker Muscular Dystrophy

Intervention / Treatment
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* Genetic: Genetic characterization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Cohort A requires a genetically confirmed mutation in the DMD gene with an affected child Cohort B includes DMD/BMD mothers with NO somatic mutation in the DMD gene Cohort C age-matched healthy controls with a normal CK level Cohort D requires a genetically confirmed mutation in the DMD gene without an affected child Able to complete testing in English Able to consent Exclusion Criteria: Subjects with a contraindication to cardiac or skeletal muscle MRI Subjects on heart failure medication at time of enrollment Subjects on steroid treatment Presence of an inherited neurologic disease or comorbidity that may affect their ability to complete this study Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Cohort A<br>DMD/BMD Female Carriers who have/had an affected child (n=150) | Genetic: Genetic characterization<br>* Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts<br>|
| Cohort B<br>DMD/BMD Female non-carriers controls who have/had an affected child (n=50) | Genetic: Genetic characterization<br>* Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts<br>|
| Cohort C<br>Healthy Age-Matched Controls (n=50) | Genetic: Genetic characterization<br>* Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts<br>|
| Cohort D<br>DMD/BMD Female Carriers with no affected children (n=25) | Genetic: Genetic characterization<br>* Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compromise of cardiac function based on Cardiac Magnetic Resonance Imaging | Cardiac function as compromised by evidence of scarring of cardiac muscles, particularly of the base of the left ventricle via cardiac MRI studies with gadolinium contrast. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Function Assessment Treadmill SVO2 | Stress on heart muscle measured by SVO2 (percentage of oxygen saturation in the blood of the pulmonary artery). SVO2 represents an average of all the venous oxygen saturation of major organs and tissues. This measure provides assessment of cardiopulmonary function and helps measure the degree of cardiac instability and can be an indicator of deterioration from normal. | 2 years | 
| Physical Therapy Assessments Maximum Voluntary Isometric Contraction Testing | MVICT measures strength of skeletal muscles by assessing the force generated by by individual muscles. The results can be compared to norms and deterioration can be assessed over time. | 2 Years | 
| Physical Therapy Assessments 6 Minute Walk Test | A timed test to assess distance walked in 6 minutes is very quantitative and can be assessed in comparison to normal controls. Deterioration over time can be clearly measured. | 2 years | 
| Physical Therapy Assessments ACTIVE-seated | Exploratory outcome quantifying upper extremity reaching ability using a custom-designed game telling how far the arm reaches in comparison to overall functional ability of the individual ability. | 2 Years | 
| Physical Therapy Assessments Time-to-Rise | A timed-test to measure ability to rise from the floor is quantifiable and measuring over time tells if there is loss of function. | 2 Years | 
| Laboratory biomarkers - Creatine Kinase | CK levels are an indicator of muscle breakdown. | 2 Years | 
| Laboratory biomarkers - C-Reactive Protein | Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown. | 2 Years | 
| Laboratory biomarkers - Interleukin-6 | Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown. | 2 Years | 
| Laboratory biomarkers - Cortisol levels | Hair cortisol levels measure stress levels as a means of understanding coping with disease. | 2 Years | 
| Cognitive Assessment | Cognitive function measured by Wechsler Abbreviated Scale of Intelligence (WASI) provides a possible tool to measure disease awareness and establish if IQ level correlates with disease-related stress. | 2 Years | 
| Caregiver Stress | Online self-report survey to assess stress burden on caregiver. | 2 Years | 
| Pulmonary function testing (PFTs) | Stable or improved FVC | 2 Years |