Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials |
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| Affiliation: | 1. Memory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA;2. Department of Epidemiology and Biostatistics, Division of Biostatistics, University of California San Francisco, 550 16th Street, San Francisco, CA, 94158, USA;3. Department of Neurology, University of Toronto, 399 Bathurst St, McLaughlin 7-418, Toronto, ON, M5T 2S8, Canada;4. Department of Neurology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA;5. Department of Neurology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA;6. Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;7. Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;8. Department of Neurology, Baylor College of Medicine, 6550 Fannin St # 1801, Houston, TX, 77030, USA;9. Institute of Neurology, University College of London, 1 Wakefield Street, London, WC1N 1PJ, UK;10. UCB BioSciences, Research Triangle, NC, USA;11. Celerion, 621 Rose St, Lincoln, NE, 68502, USA;1. Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Kateřinská 30, 128 21, Prague, Czech Republic;2. Department of Nursing, Faculty of Health Science, Palacky University Olomouc, Tř. Svobody 8, 771 11, Olomouc, Czech Republic;3. Department of Radiology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Kateřinská 30, 128 21, Prague, Czech Republic;4. Institute of Neuropsychiatric Care (INEP), Křižíkova 264/22, 186 00, Prague, Czech Republic;5. 4th Department of Internal Medicine, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, U Nemocnice 2, 128 08, Prague, Czech Republic;6. Department of Pediatrics and Adolescent Medicine, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Ke Karlovu 2, 121 00, Prague, Czech Republic;7. Institute of Neuroradiology, Universitaetsmedizin Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany;1. Neurology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy;2. IRCSS Santa Lucia, Rome, Italy;3. Institute of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy;4. Don Carlo Gnocchi Onlus Foundation, Milan, Italy;5. Department of Biopathology and Diagnostic Imaging, University of Rome Tor Vergata, Rome, Italy;6. Stroke Unit, Policlinico Tor Vergata, Rome, Italy |
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| Abstract: | IntroductionClinical 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.MethodsLongitudinal 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).ResultsBaseline 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.ConclusionBaseline 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. |
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| Keywords: | Progressive supranuclear palsy Clinical trial methodology |
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