Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

AL-108-231 Investigators

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalParkinsonism and Related Disorders
Volume28
DOIs
StatePublished - Jul 1 2016

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Progressive Supranuclear Palsy
Multicenter Studies
Disease Progression
Clinical Trials
Executive Function
Primary Spontaneous Pneumothorax
Phase III Clinical Trials
Aptitude
Neuropsychological Tests
Mesencephalon
Cognition
Color
Depression

Keywords

  • Clinical trial methodology
  • Progressive supranuclear palsy

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials. / AL-108-231 Investigators.

In: Parkinsonism and Related Disorders, Vol. 28, 01.07.2016, p. 41-48.

Research output: Contribution to journalArticle

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title = "Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials",
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.",
keywords = "Clinical trial methodology, Progressive supranuclear palsy",
author = "{AL-108-231 Investigators} and Jee Bang and Lobach, {Iryna V.} and Lang, {Anthony E.} and Murray Grossman and Knopman, {David S.} and Miller, {Bruce L.} and Schneider, {Lon S.} and Doody, {Rachelle S.} and Andrew Lees and Michael Gold and Morimoto, {Bruce H.} and Boxer, {Adam L.} and David Williams and Lafontaine, {Anne Louise} and Connie Marras and Mandar Jog and Michael Panisset and Anthony Lang and Lesley Parker and Stewart, {Alistair J.} and Corvol, {Jean Christophe} and Azulay, {Jean Philippe} and Philippe Couratier and Brit Mollenhauer and Stefan Lorenzl and Albert Ludolph and Reiner Benecke and Gunter Hoglinger and Axel Lipp and Heinz Reichmann and Dirk Woitalla and Dennis Chan and Adam Zermansky and David Burn and Illana Gozes and Erik Roberson and Lawrence Honig and Edward Zamrini and Rajesh Pahwa and Yvette Bordelon and Erika Driver-Dunkley and Stephanie Lessig and Mark Lew and Kyle Womack and Brad Boeve and Joseph Ferrara and Argyle Hillis and Daniel Kaufer and Rajeev Kumar and Tao Xie",
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AU - AL-108-231 Investigators

AU - Bang, Jee

AU - Lobach, Iryna V.

AU - Lang, Anthony E.

AU - Grossman, Murray

AU - Knopman, David S.

AU - Miller, Bruce L.

AU - Schneider, Lon S.

AU - Doody, Rachelle S.

AU - Lees, Andrew

AU - Gold, Michael

AU - Morimoto, Bruce H.

AU - Boxer, Adam L.

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 - Hoglinger, Gunter

AU - Lipp, Axel

AU - Reichmann, Heinz

AU - Woitalla, Dirk

AU - Chan, Dennis

AU - Zermansky, Adam

AU - Burn, David

AU - Gozes, Illana

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

PY - 2016/7/1

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N2 - 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.

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KW - Clinical trial methodology

KW - Progressive supranuclear palsy

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