A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease for which no
curative treatment has yet been identified, making it important to slow progression and
improve the quality of life among affected boys and young men. Treatment with
corticosteroids is standard of care for patients with DMD five years old and older, due to
the robust observation that this intervention lengthens the interval prior to loss of
ambulation but is associated with many side effects. This clinical trial will be conducted
in the youngest age group able to receive corticosteroids orally and on whom study outcomes
are measurable, ages 3 to 7 years. This is a randomized, double blinded, double masked,
placebo-controlled clinical trial that will explore whether better synchronization of
corticosteroid administration with the circadian rhythm will provide improved tolerability
and at least comparable efficacy to current standards in which corticosteroids are always
given in the morning. Furthermore, the trial provides a unique opportunity to rigorously
evaluate corticosteroid effects in the young DMD patient, both for efficacy as compared to
placebo and as a study of the impact of corticosteroid chronotherapy, or delayed release, on
increased tolerability over standard therapy. The main hypothesis is that synchronization of
the timing of corticosteroid dosing will improve medication tolerability in children, while
maintaining (non-inferiority) the efficacy of corticosteroid. The study also offers a
unique opportunity to measure several biomarkers as well as novel genetic modifiers that may
further impact the response to corticosteroid in DMD.