Feasibility and efficacy of exercise training on sleep symptoms and comorbidities in narcolepsy type 1: a prospective interventional study

Current treatments for narcolepsy type 1 (NT1) have little impact on psychiatric, cognitive, and metabolic comorbidities. Here, we evaluated the feasibility, safety, and efficacy of a prospective exercise training (ET) program on sleep-related symptoms and comorbidities in NT1. Sedentary adult with NT1 participated in a 6-week supervised ET program followed by a 18-week self-directed program. Outcomes included the Narcolepsy Severity Scale (NSS), Hospital Anxiety and Depression Scale, Insomnia Severity Index (ISI), cardiometabolic parameters (body mass index [BMI], glycemia, insulin, C-reactive protein, lipid panel with insulin resistance [IR] [TG/HDL-C] and cardiovascular risk [Total-C/HDL-C] markers), cardiorespiratory fitness, and attention (Bron/Lyon Attention Stability Test). Wilcoxon tests compared baseline, 6-week, and 6-month data. Among 30 participants (73.3% women, 39.8 ± 13.9 years, BMI = 31.0 ± 5.1 kg/m2), 25 completed the 6-month program. Of the 379 supervised sessions (84.2% attendance), only seven partial cataplexies occurred. At 6 weeks, significant improvements were observed in median[IQR] NSS (-2.0[-4.0;0], p=.046), ISI (-1.0[-3.0;1.0], p=.050), triglycerides (-0.21[-0.46;-0.09]g/L, p=.015), IR (-0.19[-0.46;-0.04], p=.003), cardiorespiratory fitness (+15.0[5.0;20.0]watts, p<.001), and in most attention scores (stability, intensity, reaction time: p<.05). At 6 months, NSS and ISI changes were no longer significant but anxiety (-1.0[-3.0;1.0], p=.041) and depression (-2.0[-4.0;0.0], p=.004) decreased. Improvements in IR (-0.27[-0.44;-0.11], p=.002), triglycerides (-0.2[-0.4;0.0]g/L, p=.033), cardiovascular risk (-0.16[-0.41;-0.02], p=.019), and attention scores (intensity, reaction time, number of errors p<.05) were sustained. VO2max and BMI showed no significant changes. Physical activity is feasible and safe in NT1, enabling improvements in narcolepsy symptoms, anxiety/depression, cognition, and cardiometabolic markers. Larger randomized controlled trials are needed to confirm these findings. Clinical Trial: NARCOSPORT NCT05460052.