Validation of Functional Reaching Volume as an Outcome Measure across the Spectrum of Abilities in Muscular Dystrophy
Abstract
The success or failure of a clinical trial depends on the efficacy of the compound and the appropriateness and sensitivity of the primary endpoint. For the first time in multiple decades, potential treatments are on the horizon for individuals with dystrophinopathies. However, enrollment in clinical trials is often dependent on the ability to walk as this is the primary efficacy outcome, which excludes a substantial population who no longer walk but are eager to participate. Also, if subjects lose the ability to walk during a clinical trial, the future data are lost. The objective of this proposal is to produce a distributable, clinical trial-ready outcome measure that will improve functional assessments and increase the potential enrollment pool for clinical trials in Duchenne Muscular Dystrophy (DMD). To address this void, we developed a custom-designed video game, called ACTIVE, to quantify the ability to interact with the environment, also known as functional reaching volume (FRV), as the participant either hunts for gems or squishes spiders. While the subject plays the engaging game, the skeletal tracking algorithm from the Microsoft Kinect camera is used to determine the furthest arm excursion in six three-dimensional quadrants. This proposal addresses two of the Fiscal Year 2015 Duchenne Muscular Dystrophy Research Program Focus Areas: (1) Discovery and qualification of predictive biomarkers, e.g., drug development tools or clinical trial outcomes and (2) Assessment of clinical trial outcomes such as evaluating surrogate markers and patient-centered outcomes. The Center for Drug Evaluation and Research drug development tool committee responded favorable to our initial briefing package and the advice received was used to formulate this proposal. Data from this proposal will be submitted as part of our qualification package. As demonstrated by our pilot data s high correlation between parent-reported measures of activities of daily living and ACTIVE scores, this data is extremely important to patients as it is directly related to their ability to perform these meaningful activities. Despite our encouraging preliminary data, we have identified some limitations in ACTIVE s ability to be used across the spectrum of abilities in DMD. As weakness progresses, adolescents and adults arm function is limited to small wrist and finger movements. Our current system has difficulty recognizing these small movements. To ensure trial access to all individuals, we are partnering with a colleague that has developed miniature wireless motion capture sensors, known as Solitons, that pair with custom therapeutic software. This system is ideally suited for immediate implementation into the ACTIVE system. Use of the Solitons will completely remove the aforementioned shortcomings in the current system as they are able to track very small movements (<0.5 degrees). Solitons are about the size and weight of a US quarter, and have up to 6 hours of rechargeable battery life. To test the efficacy of Solitons, we will utilize our large clinic population (300 patients with dystrophinopathy seen last year) to establish the natural rate of change in 6 months in a sample of 72 boys with DMD and 72 age-matched controls. Patients attend clinic visits every 6 months and complete ACTIVE testing as part of our standard clinic evaluation. Over the 2-year period of this grant, we estimate cross-sectional sample of 140 patients, and longitudinal sample of 87 patients with 6-month visits, and 60 patients with 12-month visits (assuming a 10% drop-out) using the Soliton system alongside the current ACTIVE system to compare results of both systems across the spectrum of disease. Validating ACTIVE as an outcome measure across the span of abilities in muscular dystrophy will advance the field of DMD research by improving functional assessments and increasing the participant pool in clinical trials and improve patient care by allowing
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610305
Entities
People
- Linda Lowes
Organizations
- United States Army