P.7.1 A prospective natural history study of the progression of physical impairment, activity limitation, and quality of life in Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is characterized by a progressive and irreversible loss in muscle function, with a predictable sequence of loss of ambulation and upper limb function followed by cardiorespiratory failure. There is currently no cure; however, a multidisciplinary approach to the symptoms and the use of corticosteroids has been shown to delay disease progression and is recommended as standard of care. Within the patient population, decreased muscle function and age at loss of ambulation and cardiorespiratory functions are highly variable. This study aims to describe contemporary natural history in the steroid era by measuring muscle strength and function over time, assessing quality of life (QoL), and measuring biomarkers in patients with DMD. A total of 250 boys with DMD (aged 3–18 years), both ambulant and non-ambulant, are planned to be enrolled at 16 sites across 10 countries and followed every 6 months for 3 years. Standardized outcome measures, including the 6-min walk test, timed tests, North Star Ambulant Assessment, Performance of Upper Limb, pulmonary function testing, and QoL surveys, as well as new exploratory measures, will be assessed by experienced clinical evaluators. Blood and urine samples are to be collected to test biomarkers of disease progression and imaging will be performed by magnetic resonance imaging/magnetic resonance spectroscopy at selected sites. Mutations affecting the DMD gene and concomitant medications will also be recorded. Longitudinal data will also be obtained, including 6-min walk distance, muscle function scores, pulmonary function results, and scores in QoL surveys. Outcome measurements are planned to be assessed by a number of factors, including mutation type and age group. The measures obtained will give a clear picture of the evolution of muscle function and disease progression that could be used as surrogate placebo data in clinical trials involving investigational drugs.