Clinical efficacy of NIV and modafinil on excessive daytime sleepiness: a multicenter, randomized, double-blind, placebo-controlled clinical trial in DM1

Excessive Daytime Sleepiness (EDS) is amongst the most frequent complaints in Myotonic Dystrophy type 1 (DM1), the most frequent muscular dystrophy of adulthood. EDS is mostly of central origin in DM1 but, at least part of it, is related to symptoms of chronic respiratory insufficiency, which can be corrected by NIV. Modafinil, has reduced EDS in some patients with DM1. However, data are limited and there is yet no consensus on the treatment of EDS in these patients. This is a multicenter, placebo-controlled, randomized trial to test clinical efficacy of nocturnal non-invasive ventilation (NIV) and modafinil on EDS in DM1. The primary outcome of the study will be the objective reduction of EDS as assessed by the Maintenance of Wakefulness Test. Secondary outcomes will be the patient-reported reduction of EDS; maintainance of respiratory function; improvement on cognitive tests and function; reduction in fatigue perception; improved quality of life (QoL) perception; improved motor function and improved compliance to NIV. One-hundred patients from two Neuromuscular Units (the NEMO Center in Milan and the Neuromuscular Center in Tor Vergata, Rome) will be subjected to Multiple Sleep Latency Test (MSLT) to screen for EDS and to respiratory assessments to determine indications for NIV. Recruitment will occur in year 1. Eighty consecutive patients with EDS will be eligible and will be randomized to modafinil or placebo. The portion of patients with EDS and indications for NIV will be randomized to either modafinil or placebo after 1 month NIV optimization and will maintain NIV for the whole study period. Respiratory assessments and EDS will be assessed at 3 months and at 6 months. Quality of life and cognitive impairment will be determined prior to randomization and at the end of each study period, at 3 and 6 months. Data collection and analysis will occur during the whole study period and will end by year 2.