Establishing the validity of motor outcome measures in young boys with Duchenne Muscular Dystrophy is critical for the success of future trials

by Dr. Melissa McIntyre

Publication:
Natural History of Steroid-Treated Young Boys With Duchenne Muscular Dystrophy Using the NSAA, 100m, and Timed Functional Tests
Natalie F. Reash (Miller) et al.
Pediatric Neurology Dec 2020
https://pubmed.ncbi.nlm.nih.gov/32979653/

Summary

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder characterized by progressive deterioration and resulting weakness in skeletal, respiratory, and cardiac muscles. There are many ongoing and upcoming clinal trials assessing the efficacy of novel treatments for those with DMD. Recent developments suggest that potential treatments may offer greater benefit early in the disease process. Measuring response to treatment in young males with DMD is confounded because young boys with DMD are expected to gain new motor skills until approximately seven years of age, despite their diagnosis and underlying muscle weakness.

The authors sought to document the expected natural history for 3-8 year old boys with DMD on a stable glucocorticoid treatment, as measured by the North Star Ambulatory Assessment (NSAA), 100-meter timed test (100m), timed function tests (TFT). TFT's include time to climb four stairs (4SC), time to stand from supine (Rise), time to walk/run 10-meters (10m).

One hundred sixty-two boys with DMD aged 3-8 years on glucocorticoids were evaluated using one or more of the described with follow-up measures taken on a subcohort at 12 months. Developmental gains were noted for all tests in the cross-sectional cohort until approximately 6-7 years of age. Average scores and times are presented by age group for all outcomes for cohort-level comparison.  .All subjects took significantly longer to traverse 100 meters compared to published normative data. TFT's utility was limited in this cohort, with 43%, 66%, and 82% of the cohort completing 10m, Rise, and 4SC in less than five seconds which would indicate a strong ceiling effect in this age group. Additionally, all TFTs changed one second or less at 12-month follow-up, making it difficult to distinguish true, meaningful change. At 12 month follow-up, a small group change that trended toward improvement was seen for NSAA, 100m, and 100m percent predicted. Changes were most pronounced for the children who were 3 or 4 at the time of enrollment.

In summary, commonly used outcome measures for DMD appear valuable and feasible in younger cohorts. This study documents baseline and 12 months change of boys with DMD receiving a stable dose of corticosteroids between 3-8 years of age. The NSAA and 100m are least likely to demonstrate a ceiling effect and appear more sensitive to change over time, so would be recommended for use in this cohort. As developmental gains and subsequent improvement on motor outcomes measures are expected in this younger population, these data will be useful when comparing ongoing and future therapeutic interventions for DMD.

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About the Author

I obtained my Doctorate of physical therapy degree from The Ohio State University in 2015 and serve as a research physical therapist in the Center for Gene Therapy at Nationwide Children’s Hospital. My research focuses on clinical trial readiness through appropriate outcome selection, development and validation of novel tools to reduce the burden of testing, as well as standardizing outcome administration and scoring across sites and countries participating in clinical trials.

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About the Reviewer

I received a Doctorate of Physical Therapy (DPT) from the University of Utah in 2016. I am currently pursuing a PhD in Rehabilitation Sciences at the University of Utah. I work as a physical therapist and clinical evaluator with the Utah Program for Inherited Neuromuscular Disorders (UPIN) at the University of Utah. Through UPIN, my work focuses on research and clinical care of neuromuscular disorders affecting both adult and pediatric populations.