Electrical Impedance Myography and Ultrasound as Biomarkers of Duchenne Muscular Dystrophy (QED)

Primary Outcome Measures:

• The rate of decline of DMD patients versus normal subjects as assessed by EIM and quantitative ultrasound [ Time Frame: up to 45 months ] [ Designated as safety issue: No ]
  With the successful completion of this aim, the investigators will establish that alterations in both EIM and QUS provide meaningful surrogate measures of disease progression in DMD.
  
  

Secondary Outcome Measures:

• The rate of decline of DMD patients versus normal subjects as assessed by handheld dynamometry, 6-minute walk, and other functional tests. [ Time Frame: up to 45 months ] [ Designated as safety issue: No ]
  With the successful completion of this aim, the investigators will establish that alterations in functional assessments may provide additional meaningful surrogate measures of disease progression in DMD.
  
  

Characterized by progressive disability leading to death, Duchenne muscular dystrophy (DMD) remains one of the most common and devastating neuromuscular disorders of childhood. Although a variety of promising new treatment strategies are in development, outcome measures for clinical trials remain limited for the most part to a set of functional measures, such as the six-minute walk test. While clearly useful, such measures are impacted by unrelated factors, such as mood and effort, and have limited repeatability. To address this and other limitations, magnetic resonance imaging (MRI) is now being investigated as a surrogate measure. However, more easily applied, cost-effective, office-based surrogate measures that provide high repeatability and sensitivity while still correlating strongly to disease status would find wider use in Phase II and possibly in Phase III clinical trials in DMD. Quantitative ultrasound (QUS) and electrical impedance myography (EIM) are two techniques that could serve in this role. In QUS, muscle pathology (fibrosis and fatty infiltration) in DMD results in an increase in energy reflected back (backscatter) to the ultrasound. The amount of backscatter can be measured directly by analyzing the raw frequency-based acoustic data or indirectly by controlled processing of the gray-scale image. EIM, in contrast, relies upon the application of localized electrical current and measurement of the resulting surface voltages, but is similarly impacted by the fibrotic changes that develop as muscle disease progresses. Here, the investigators propose to evaluate and compare both methodologies simultaneously in a group of DMD patients and normal subjects in order to assess their ability to identify clinically meaningful alterations in muscle health over short intervals of time. As a final exploratory analysis, the investigators will also study the possibility of combining the two modalities. The results of this work will have broad application as they could be applied to a variety of neuromuscular conditions, including other muscular dystrophies. Thus, the hypothesis of this proposal is that both QUS and EIM can serve as convenient, non-invasive, clinically meaningful surrogate markers of disease progression in DMD that surpass the functional measures currently in use.