TY - JOUR
T1 - Magnetic Resonance Imaging Measures to Track Atrophy Progression in Progressive Supranuclear Palsy in Clinical Trials
AU - the AL-108-231 Investigators, the Tauros MRI Investigators, the PASSPORT Study Group, the DESCRIBE-PSP Group
AU - Quattrone, Andrea
AU - Franzmeier, Nicolai
AU - Huppertz, Hans Jürgen
AU - Klietz, Martin
AU - Roemer, Sebastian N.
AU - Williams, David
AU - Lafontaine, Anne Louise
AU - Marras, Connie
AU - Jog, Mandar
AU - Panisset, Michael
AU - Lang, Anthony
AU - Parker, Lesley
AU - Stewart, Alistair J.
AU - Corvol, Jean Christophe
AU - Azulay, Jean Philippe
AU - Couratier, Philippe
AU - Mollenhauer, Brit
AU - Lorenzl, Stefan
AU - Ludolph, Albert
AU - Benecke, Reiner
AU - Höglinger, Günter
AU - Lipp, Axel
AU - Reichmann, Heinz
AU - Woitalla, Dirk
AU - Chan, Dennis
AU - Zermansky, Adam
AU - Burn, David
AU - Lees, Andrew
AU - Boxer, Adam
AU - Miller, Bruce L.
AU - Lobach, Iryna V.
AU - Roberson, Erik
AU - Honig, Lawrence
AU - Zamrini, Edward
AU - Pahwa, Rajesh
AU - Bordelon, Yvette
AU - Driver-Dunkley, Erika
AU - Lessig, Stephanie
AU - Lew, Mark
AU - Womack, Kyle
AU - Boeve, Brad
AU - Ferrara, Joseph
AU - Hillis, Argyle
AU - Kaufer, Daniel
AU - Kumar, Rajeev
AU - Xie, Tao
AU - Gunzler, Steven
AU - Zesiewicz, Theresa
AU - Dayalu, Praveen
AU - Priller, Josef
N1 - Publisher Copyright:
© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2024/8
Y1 - 2024/8
N2 - Background: Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed. Objective: Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials. Methods: Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) patients with one-year-follow-up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age-matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas-based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data. Results: Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems. Conclusions: This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas-based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects.
AB - Background: Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed. Objective: Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials. Methods: Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) patients with one-year-follow-up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age-matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas-based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data. Results: Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems. Conclusions: This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas-based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects.
KW - atlas-based volumetry
KW - clinical trials
KW - progression
KW - progressive supranuclear palsy
KW - staging system
UR - http://www.scopus.com/inward/record.url?scp=85195822733&partnerID=8YFLogxK
U2 - 10.1002/mds.29866
DO - 10.1002/mds.29866
M3 - Article
C2 - 38825840
AN - SCOPUS:85195822733
SN - 0885-3185
VL - 39
SP - 1329
EP - 1342
JO - Movement Disorders
JF - Movement Disorders
IS - 8
ER -