Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

• Published in: Parkinsonism & related disorders Vol. 28; pp. 41 - 48
• Main Authors: Bang, Jee, Lobach, Iryna V, Lang, Anthony E, Grossman, Murray, Knopman, David S, Miller, Bruce L, Schneider, Lon S, Doody, Rachelle S, Lees, Andrew, Gold, Michael, Morimoto, Bruce H, Boxer, Adam L
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2016
• Subjects: Clinical trial methodology; Clinical Trials as Topic - statistics & numerical data; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multicenter Studies as Topic - statistics & numerical data; Neurology; Outcome Assessment (Health Care) - statistics & numerical data; Patient Dropouts - statistics & numerical data; Prognosis; Progressive supranuclear palsy; Supranuclear Palsy, Progressive - diagnosis; Supranuclear Palsy, Progressive - diagnostic imaging; Supranuclear Palsy, Progressive - physiopathology; Progressive supranuclear palsy; Clinical trial methodology
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2016.04.014

Abstract Introduction Clinical and MRI measurements can track disease progression in PSP, but many have not been extensively evaluated in multicenter clinical trials. We identified optimal measures to capture clinical decline and predict disease progression in multicenter PSP trials. Methods Longitudinal clinical rating scales, neuropsychological test scores, and volumetric MRI data from an international, phase 2/3 clinical trial of davunetide for PSP (intent to treat population, n = 303) were used to identify measurements with largest effect size, strongest correlation with clinical change, and best ability to predict dropout or clinical decline over one year as measured by PSP Rating Scale (PSPRS). Results Baseline cognition as measured by Repeatable Battery for Assessing Neuropsychological Status (RBANS) was associated with attrition, but had only a small effect. PSPRS and Clinical Global Impression (CGI) had the largest effect size for measuring change. Annual change in CGI, RBANS, color trails, and MRI midbrain and ventricular volumes were most strongly correlated with annual PSPRS and had the largest effect sizes for detecting annual change. At baseline, shorter disease duration, more severe depression, and lower performance on RBANS and executive function tests were associated with faster worsening of the PSPRS in completers. With dropouts included, SEADL, RBANS, and executive function tests had significant effect on PSPRS trajectory of change. Conclusion Baseline cognitive status and mood influence the rate of disease progression in PSP. Multiple clinical, neuropsychological, and volumetric MRI measurements are sensitive to change over one year in PSP and appropriate for use in multicenter clinical trials.