Video Game Technology Could Expand Clinical Trials Eligibility For Persons With Duchenne Muscular Dystrophy

Researchers at Nationwide Children’s Hospital in Columbus, Ohio have developed a method for measurement of upper extremity movement in muscular dystrophy patients that employs interactive video game technology. The objective is an expansion of inclusion criteria for patients using wheelchairs who participate in clinical trials.

Duchenne muscular dystrophy, the most common of several forms of the disease, is a neuromuscular disorder found only in males caused by lack of a protein called dystrophin — a condition that causes progressive muscle weakness.

The researchers report that video game scores correlate strongly with parent descriptions of patients’ daily activities, mobility and social and cognitive skills in a study published online in the peer-reviewed journal Muscle and Nerve. They note that patients with diseases like muscular dystrophy whose loss of mobility obliges them to use wheelchairs are currently excluded from clinical trials due to the lack of easy, affordable or comprehensive ways to measure their muscular function. The standard mobility demonstration measurement involves the patient in a six minute walking test. The Nationwide Children’s researchers are hopeful that the specifically-developed video game, designed with patient input, will successfully demonstrate to the U.S. Food and Drug Administration (FDA) that game play by a patient accurately yields the similar results to the walking test, as a way to quantify patient progress.

The Nationwide Children’s researchers’ findings are published in a research article published in the journal Muscle & Nerve, entitled “Reliability and validity of ACTIVE-seated: An outcome in dystrophinopathy“ (Muscle & Nerve, 2014; DOI: 10.1002/mus.24557) — coauthored by Linda P. Lowes PT, PhD (Corresponding Author), Lindsay N. Alfano DPT, PCS, and Katherine Berry PT, of The Research Institute at Nationwide Children’s Hospital, Center for Gene Therapy in Columbus, Ohio; Roger Crawfis PhD, of The Ohio State University, Department of Computer Science and Engineering in Columbus; Han Yin MS, PhD, and Igor Dvorchik PhD, of the Research Institute at Nationwide Children’s Hospital’s Biostatistics Core; with Kevin M Flanigan MD, and Jerry R Mendell MD, of the Ohio State University College of Medicine, Departments of Pediatrics and Neurology at Columbus.

The coauthors note that traditional upper extremity treatment interventions typically focus on distal abilities, and don’t address quantification of the unique progression of decline in dystrophinopathy. The Nationwide Children’s researchers designed the game-based protocol they call “Ability Captured Through Interactive Video Evaluation (ACTIVE)-seated” in order to address this unmet need, with their objective to establish its validity and reliability as a measurement tool.

ACTIVE-seated technology utilizes a Kinect gaming camera of the type found in Xbox consoles, and features a patient-requested zombie theme that requires players boys to reach with their arms in various directions to push forward a force field. The Kinect camera and ACTIVE-seated software measures how far and how long the boys reach. Measuring change over time is a primary goal. The development of the game relied almost entirely on the patients.Microsoft’s Kinect gaming interface to quantify a subject’s functional reaching ability while playing a custom-designed game. A skeletal tracking algorithm was used to determine the furthest arm excursion in all planes in 61 subjects with dystrophinopathy and 16 controls.

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The scientists report that reachable area was scaled, based on arm length to standardize comparisons across subjects and to accommodate growth, noting that ACTIVE-seated discriminately ranked subjects from normal controls and by Brooke level. Scores were rigorously correlated with parent reports of daily activities and mobility, and they assess test-retest reliability of ACTIVE-seated as excellent

The researchers conclude that initial evaluation of reliability and validity suggests that ACTIVE-seated shows promise as a clinical and research outcome for individuals with dystrophinopathy.

“We were thrilled with the results,” says Dr. Linda Lowes, who is clinical therapies research coordinator for the Nationwide Children’s neuromuscular program, noting that “It’s very reliable day to day because it’s just fun. The scores are related to function, and really reflect what the boys could do in their life.”

“The game allows them to disintegrate aliens, which they love,” explains Lindsay Alfano, a physical therapist at Nationwide Children’s. “In clinical trials we need to see that they’re getting better with all of their activities. They have to spend hours with us doing nothing that’s easy, only hard things. Looking at their faces after they play this game where they get to just play and be kids is a lot of fun to see.”

Ms. Alfano and Dr. Lowes both emphasize the importance of motivation when it comes to success playing the game’s. If there is little motivation for the patient to engage in activity day after day, their performance will be affected, rendering the assessment tool useless since it would not be measuring true function potential. Therefore, finding motivational factors yields the best outcome measure.

Sixty-one patients, recruited from the Nationwide Children’s Hospital Muscular Dystrophy Association Clinic, participated in the study. Reachable area was visually represented as a series of boxes appearing on a screen, and converted to a scaled score based on arm length, which allowed for standardized comparisons among different sized patients and accommodation of patient growth. Placement of the boxes is based on the patient’s size.

“We developed this game because there was not an accepted outcome measure for boys with muscular dystrophy who couldn’t walk. So we needed an outcome measure that would be reliable, valid, and also give discrete quantitative measurements so they could measure small change or big change over time,” explains Dr. Lowes.

The study focused on patients with Duchenne Muscular Dystrophy, which is not evident at birth, with the male child born apparently healthy, but over time, parents will notice he is no longer to keep up with peers. Children with Duchenne weaken over time, gradually losing the ability to feed themselves, move normally and execute various other tasks. Affected children are usually in wheelchairs around age 12, and later in life will progressively lose respiratory and cardiovascular function. The researchers hope that the ACTIVE-seated technology can also prove effective for patients with other mobility-inhibiting conditions such as cerebral palsy.

“As a clinical trial outcome measure, we really wanted this to be as universal as possible. We want to be able to use this across sites, both in the U.S. and internationally, because most of the clinical trials are international at this point,” says Ms. Alfano. “Having something that’s commercially available, low cost and easy to implement was really a huge goal for us.”

This study was funded by the Department of Technology Development and Commercialization in the Research Institute at Nationwide Children’s Hospital, which has been ranked in the U.S.News & World Report’s “America’s Best Children’s Hospitals”, and among the top 10 for National Institutes of Health funding among free-standing children’s hospitals, sees nearly 1 million patients annually, and anchors one of the country’s largest not-for-profit freestanding pediatric health care networks. The hospital’s nearly 10,000 hospital staff and 1,000 medical staff have been providing care since 1892.

Sources:
Nationwide Children’s Hospital
Muscular Dystrophy.org
Wikipedia