Selection of Clinical Outcome Assessments for Trial Readiness in ARSACS - 2-year Progression and Responsiveness to...

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is among the most prevalent types of recessive ataxia worldwide. Given the accelerated therapeutic advances for many ataxias, there is a need to improve trial readiness. This study aimed to document the progression of balance, lower limb coordination and mobility in adults with ARSACS according to their mobility stage (walker or not) over the trial-relevant time frame of two years, and responsiveness to change of related clinical outcome assessments (COAs). Sixty participants from two neuromuscular clinics (Saguenay and Québec City, Canada) were included. The COAs were the Lower Extremity Motor Coordination Test (LEMOCOT), Co-contraction index, 30-s Chair Stand test (30 s-CST), Timed Up & Go test (TUG), 10-Meter Walk Test (10mWT), Berg Balance Scale (BBS), and Activities-specific Balance Confidence-simplified (ABC-S) scale. Responsiveness was documented using an anchor-based method with self-perception of the progression of related COA outcomes in the previous year. A significant progression above the standard error of measurement was observed for the TUG (+ 7.8 s [24% compared with baseline]), 10mWT (-0.111 to-0.165 m/s [-17 to -20%]), BBS (-4.3 points [-24%]), and ABC-S (-4.3 points [-15%]), with some differences between mobility stages; participants using a walking aid or wheelchair showed greater progression. The TUG, 10mWT, and BBS were the most sensitive to change in COAs, detecting changes specifically in participants who reported getting worse. These results are pivotal for defining inclusion criteria and selecting COAs for future clinical trials.