A Trial of Chronotherapy of Corticosteroids in Duchenne Muscular Dystrophy

CINRG0513: 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.

Inclusion Criteria:

• Genetically confirmed dystrophin mutation compatible with DMD phenotype. Specifically, gene deletion test positive (missing one or more exons) in the central rod domain (exons 25-60) of dystrophin, where reading frame can be predicted as 'out-of-frame' OR showing complete absence of dystrophin by muscle biopsy.
• Ages between 3 years and < 7 years
• Steroid-naïve
• Signed informed consent

Exclusion Criteria:

• Treatment with CoenzymeQ10, creatine, amino acid supplements within 3 months of study entry
• Treatment with cardiac medications: beta-blockers, digoxin, and carvedilol
• Existing medical condition or physical disability that would alter subject's motor development
• Existing medical condition that precludes the use of corticosteroids
• Inability to swallow sample tablet in bite of soft food*
• Investigator assessment that participant or family will not be compliant with treatment or study procedures
• Been on investigational DMD medication for the past 6 months