Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

Jee Bang; Iryna V. Lobach; Anthony E. Lang; Murray Grossman; David S. Knopman; Bruce L. Miller; Lon S. Schneider; Rachelle S. Doody; Andrew Lees; Michael Gold; Bruce H. Morimoto; Adam L. Boxer; David Williams; Anne Louise Lafontaine; Connie Marras; Mandar Jog; Michael Panisset; Anthony Lang; Lesley Parker; Alistair J. Stewart; Jean Christophe Corvol; Jean Philippe Azulay; Philippe Couratier; Brit Mollenhauer; Stefan Lorenzl; Albert Ludolph; Reiner Benecke; Gunter Hoglinger; Axel Lipp; Heinz Reichmann; Dirk Woitalla; Dennis Chan; Adam Zermansky; David Burn; Illana Gozes; Erik Roberson; Lawrence Honig; Edward Zamrini; Rajesh Pahwa; Yvette Bordelon; Erika Driver-Dunkley; Stephanie Lessig; Mark Lew; Kyle Womack; Brad Boeve; Joseph Ferrara; Argyle Hillis; Daniel Kaufer; Rajeev Kumar; Tao Xie; Steven Gunzler; Theresa Zesiewicz; Praveen Dayalu; Lawrence Golbe; Joseph Jankovic; Scott McGinnis; Anthony Santiago; Paul Tuite; Stuart Isaacson; Julie Leegwater-Kim; Irene Litvan; Lawrence I. Golbe; Erik D. Roberson; Mary Koestler; Clifford R. Jack; Viviana Van Deerlin; Christopher Randolph; Steve Whitaker; Joe Hirman

doi:10.1016/j.parkreldis.2016.04.014

Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

Jee Bang, Iryna V. Lobach, Anthony E. Lang, Murray Grossman, David S. Knopman, Bruce L. Miller, Lon S. Schneider, Rachelle S. Doody, Andrew Lees, Michael Gold, Bruce H. Morimoto, Adam L. Boxer, David Williams, Anne Louise Lafontaine, Connie Marras, Mandar Jog, Michael Panisset, Anthony Lang, Lesley Parker, Alistair J. StewartJean Christophe Corvol, Jean Philippe Azulay, Philippe Couratier, Brit Mollenhauer, Stefan Lorenzl, Albert Ludolph, Reiner Benecke, Gunter Hoglinger, Axel Lipp, Heinz Reichmann, Dirk Woitalla, Dennis Chan, Adam Zermansky, David Burn, Illana Gozes, Erik Roberson, Lawrence Honig, Edward Zamrini, Rajesh Pahwa, Yvette Bordelon, Erika Driver-Dunkley, Stephanie Lessig, Mark Lew, Kyle Womack, Brad Boeve, Joseph Ferrara, Argyle Hillis, Daniel Kaufer, Rajeev Kumar, Tao Xie, Steven Gunzler, Theresa Zesiewicz, Praveen Dayalu, Lawrence Golbe, Joseph Jankovic, Scott McGinnis, Anthony Santiago, Paul Tuite, Stuart Isaacson, Julie Leegwater-Kim, Irene Litvan, Lawrence I. Golbe, Erik D. Roberson, Mary Koestler, Clifford R. Jack, Viviana Van Deerlin, Christopher Randolph, Steve Whitaker, Joe Hirman

Neurology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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 language	English (US)
Pages (from-to)	41-48
Number of pages	8
Journal	Parkinsonism and Related Disorders
Volume	28
DOIs	https://doi.org/10.1016/j.parkreldis.2016.04.014
State	Published - Jul 1 2016

Bibliographical note

Funding Information:
David Knopman: Dr. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer’s Disease Cooperative Study; and receives research support from the NIH.

Funding Information:
Supported by R01AG038791, U54NS092089, T32 AG23481, and the Tau Consortium . These sources had no involvement in the study design. The funding for AL-108-231 was provided by Allon Therapeutics Inc.

Publisher Copyright:
© 2016 Elsevier Ltd.

Keywords

Clinical trial methodology
Progressive supranuclear palsy

Publisher link

10.1016/j.parkreldis.2016.04.014

http://europepmc.org/articles/pmc4914418

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Bang, J., Lobach, I. V., Lang, A. E., Grossman, M., Knopman, D. S., Miller, B. L., Schneider, L. S., Doody, R. S., Lees, A., Gold, M., Morimoto, B. H., Boxer, A. L., Williams, D., Lafontaine, A. L., Marras, C., Jog, M., Panisset, M., Lang, A., Parker, L., ... Hirman, J. (2016). Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials. Parkinsonism and Related Disorders, 28, 41-48. https://doi.org/10.1016/j.parkreldis.2016.04.014

Bang, J, Lobach, IV, Lang, AE, Grossman, M, Knopman, DS, Miller, BL, Schneider, LS, Doody, RS, Lees, A, Gold, M, Morimoto, BH, Boxer, AL, Williams, D, Lafontaine, AL, Marras, C, Jog, M, Panisset, M, Lang, A, Parker, L, Stewart, AJ, Corvol, JC, Azulay, JP, Couratier, P, Mollenhauer, B, Lorenzl, S, Ludolph, A, Benecke, R, Hoglinger, G, Lipp, A, Reichmann, H, Woitalla, D, Chan, D, Zermansky, A, Burn, D, Gozes, I, Roberson, E, Honig, L, Zamrini, E, Pahwa, R, Bordelon, Y, Driver-Dunkley, E, Lessig, S, Lew, M, Womack, K, Boeve, B, Ferrara, J, Hillis, A, Kaufer, D, Kumar, R, Xie, T, Gunzler, S, Zesiewicz, T, Dayalu, P, Golbe, L, Jankovic, J, McGinnis, S, Santiago, A, Tuite, P, Isaacson, S, Leegwater-Kim, J, Litvan, I, Golbe, LI, Roberson, ED, Koestler, M, Jack, CR, Deerlin, VV, Randolph, C, Whitaker, S & Hirman, J 2016, 'Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials', Parkinsonism and Related Disorders, vol. 28, pp. 41-48. https://doi.org/10.1016/j.parkreldis.2016.04.014

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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 = "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 and Steven Gunzler and Theresa Zesiewicz and Praveen Dayalu and Lawrence Golbe and Joseph Jankovic and Scott McGinnis and Anthony Santiago and Paul Tuite and Stuart Isaacson and Julie Leegwater-Kim and Irene Litvan and Golbe, {Lawrence I.} and Roberson, {Erik D.} and Mary Koestler and Jack, {Clifford R.} and Deerlin, {Viviana Van} and Christopher Randolph and Steve Whitaker and Joe Hirman",

note = "Funding Information: David Knopman: Dr. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer{\textquoteright}s Disease Cooperative Study; and receives research support from the NIH. Funding Information: Supported by R01AG038791, U54NS092089, T32 AG23481, and the Tau Consortium . These sources had no involvement in the study design. The funding for AL-108-231 was provided by Allon Therapeutics Inc. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd.",

year = "2016",

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doi = "10.1016/j.parkreldis.2016.04.014",

language = "English (US)",

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pages = "41--48",

journal = "Parkinsonism and Related Disorders",

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TY - JOUR

T1 - Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

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

AU - Gunzler, Steven

AU - Zesiewicz, Theresa

AU - Dayalu, Praveen

AU - Golbe, Lawrence

AU - Jankovic, Joseph

AU - McGinnis, Scott

AU - Santiago, Anthony

AU - Tuite, Paul

AU - Isaacson, Stuart

AU - Leegwater-Kim, Julie

AU - Litvan, Irene

AU - Golbe, Lawrence I.

AU - Roberson, Erik D.

AU - Koestler, Mary

AU - Jack, Clifford R.

AU - Deerlin, Viviana Van

AU - Randolph, Christopher

AU - Whitaker, Steve

AU - Hirman, Joe

N1 - Funding Information: David Knopman: Dr. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals and the Alzheimer’s Disease Cooperative Study; and receives research support from the NIH. Funding Information: Supported by R01AG038791, U54NS092089, T32 AG23481, and the Tau Consortium . These sources had no involvement in the study design. The funding for AL-108-231 was provided by Allon Therapeutics Inc. Publisher Copyright: © 2016 Elsevier Ltd.

PY - 2016/7/1

Y1 - 2016/7/1

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.

AB - 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.

KW - Clinical trial methodology

KW - Progressive supranuclear palsy

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DO - 10.1016/j.parkreldis.2016.04.014

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AN - SCOPUS:84965181205

SN - 1353-8020

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JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

ER -

Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials

Abstract

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