Category: Parkinson’s Disease: Clinical Trials
Objective: To inform the design of randomized neuroprotective trials in prodromal Parkinson’s disease (PD) by assessing the progression of prodromal markers in idiopathic rapid eye movement behavior disorder (iRBD) over time and calculating required sample sizes.
Background: The MDS Research Criteria for Prodromal PD are a validated method of identifying those at high risk of developing synucleinopathies. These individuals are ideal candidates for neuroprotective trials; however, optimal endpoints to assess drug efficacy are not well established.
Method: We combined prospective follow-up data from 18 centers of the International RBD Study Group representing 11 countries. Polysomnogram-confirmed iRBD subjects without parkinsonism or dementia at baseline (N=1171) were assessed for prodromal PD using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and special sensory testing. Sample size requirements to demonstrate slowing of progression under 3 anticipated treatment effects (30%, 50%, and 70% slowing) over a follow-up of up to 3 years were calculated.
Results: Criteria for prodromal PD were met by 808 subjects (69.0%). Among clinical variables assessed continuously, motor variables tended to require the lowest sample sizes, ranging from 259-387 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, special sensory, and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 127 per group at 50% drug efficacy and 2-year trial duration. On time-to-event analysis, increasing trial duration from 2 to 3 years resulted in comparatively smaller sample size reductions than from 1 to 2 years.
Conclusion: This study provides validation of combined milestones of motor and cognitive decline in a large international cohort, and supports the use of these markers as endpoints for clinical trials.
To cite this abstract in AMA style:
S. Joza, M. Hu, KY. Jung, D. Kunz, P. Dusek, D. Arnaldi, B. Högl, L. Ferini-Strambi, M. Terzaghi, F. Sixel-Döring, M. Puligheddu, F. Provini, S. Lewis, J. Liu, J. Bušková, A. Nicoletti, Y. Dauvilliers, C. Bassetti, M. Lawton, HJ. Kim, JS. Sunwoo, F. Bes, K. Sonka, P. Mattioli, A. Stefani, A. Ibrahim, G. Fiamingo, B. Mollenhauer, C. Trenkwalder, M. Figorilli, P. Cortelli, L. Baldelli, K. Ehgoetz Martens, Y. Li, E. Cicero, L. Guiraud, C. Schaefer, A. Pelletier, R. Postuma. Marker Progression and Sample Sizes Estimates for Trials in Prodromal Parkinson’s Disease: A Multicenter Study [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/marker-progression-and-sample-sizes-estimates-for-trials-in-prodromal-parkinsons-disease-a-multicenter-study/. Accessed June 14, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/marker-progression-and-sample-sizes-estimates-for-trials-in-prodromal-parkinsons-disease-a-multicenter-study/