An Open Label Exploratory Clinical Trial Evaluating Safety and Tolerability of Once-Weekly Prednisone in Becker and Limb-Girdle Muscular Dystrophy.

ABSTRACT

BACKGROUND: Glucocorticoid steroids are standard of care in Duchenne Muscular Dystrophy (DMD) to slow disease course. Use of glucocorticoids in other muscular dystrophies, including Becker (BMD) and Limb Girdle (LGMD), has been less explored. Recently, preclinical studies conducted in DMD and LGMD mouse models showed once-weekly prednisone was associated with improved muscle performance without activation of muscle atrophy genes. OBJECTIVE: To determine safety and tolerability of once-weekly prednisone in patients with LGMD and BMD. METHODS: We conducted an open label, exploratory single center study of of once-weekly prednisone at 0.75-1 mg/Kg in LGMD (n = 19) and BMD (n = 1) (mean age 35, range 18-60). The LGMD participants represented multiple different LGMD subtypes, and the study included ambulatory and non-ambulatory participants. Participants were assessed at baseline and 24 weeks for vital signs, blood biomarkers, and for patient-reported side effects. As secondary endpoints, functional muscle testing and body composition were measured. RESULTS: Over the 24-week study, there were no significant changes in blood pressure, HgbA1C, or lipid profiles. We observed a reduction in serum creatine kinase over the study interval. Whole body DEXA scanning suggested a possible increase in lean mass and a reduction in adiposity. Functional measures suggested trends in improved muscle performance. CONCLUSIONS: In this single center, open label pilot study, once-weekly prednisone was safe and well tolerated. Additional investigation of once-weekly prednisone in a larger cohort and for a longer period of time is warranted.