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Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A

With therapeutic trials on the horizon for Charcot-Marie-Tooth type 1A (CMT1A), reliable, valid, and responsive clinical outcome assessments and biomarkers are essential. Accelerate Clinical Trials in CMT (ACT-CMT) is an international study designed to address important gaps in CMT1A clinical trial...

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Autores principales: Eichinger, Katy, Sowden, Janet E., Burns, Joshua, McDermott, Michael P., Krischer, Jeffrey, Thornton, John, Pareyson, Davide, Scherer, Steven S., Shy, Michael E., Reilly, Mary M., Herrmann, David N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271780/
https://www.ncbi.nlm.nih.gov/pubmed/35832173
http://dx.doi.org/10.3389/fneur.2022.930435
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author Eichinger, Katy
Sowden, Janet E.
Burns, Joshua
McDermott, Michael P.
Krischer, Jeffrey
Thornton, John
Pareyson, Davide
Scherer, Steven S.
Shy, Michael E.
Reilly, Mary M.
Herrmann, David N.
author_facet Eichinger, Katy
Sowden, Janet E.
Burns, Joshua
McDermott, Michael P.
Krischer, Jeffrey
Thornton, John
Pareyson, Davide
Scherer, Steven S.
Shy, Michael E.
Reilly, Mary M.
Herrmann, David N.
author_sort Eichinger, Katy
collection PubMed
description With therapeutic trials on the horizon for Charcot-Marie-Tooth type 1A (CMT1A), reliable, valid, and responsive clinical outcome assessments and biomarkers are essential. Accelerate Clinical Trials in CMT (ACT-CMT) is an international study designed to address important gaps in CMT1A clinical trial readiness including the lack of a validated, responsive functional outcome measure for adults, and a lack of validated biomarkers for multicenter application in clinical trials in CMT1A. The primary aims of ACT-CMT include validation of the Charcot-Marie-Tooth Functional Outcome Measure, magnetic resonance imaging of intramuscular fat accumulation as a lower limb motor biomarker, and in-vivo reflectance confocal microscopy of Meissner corpuscle sensory receptor density, a sensory biomarker. Initial studies have indicated that these measures are feasible, reliable and valid. A large prospective, multi-site study is necessary to fully validate and examine the responsiveness of these outcome measures in relation to existing outcomes for use in future clinical trials involving individuals with CMT1A. Two hundred 15 adults with CMT1A are being recruited to participate in this prospective, international, multi-center study. Serial assessments, up to 3 years, are performed and include the CMT-FOM, CMT Exam Score-Rasch, Overall Neuropathy Limitations Scale, CMT-Health Index, as well as nerve conduction studies, and magnetic resonance imaging and Meissner corpuscle biomarkers. Correlations using baseline data will be examined for validity. Longitudinal analyses will document the changes in function, intramuscular fat accumulation, Meissner corpuscle sensory receptor density. Lastly, we will use anchor-based and other statistical methods to determine the minimally clinically important change for these clinical outcome assessments and biomarkers in CMT1A. Reliable, and responsive clinical outcome assessments of function and disease progression biomarkers are urgently needed for application in early and late phase clinical trials in CMT1A. The ACT-CMT study protocol will address this need through the prospective, longitudinal, multicenter examination in unprecedented detail of novel and existing clinical outcome assessments and motor and sensory biomarkers, and enhance international clinical trial infrastructure, training and preparedness for future therapeutic trials in CMT and related neuropathies.
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spelling pubmed-92717802022-07-12 Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A Eichinger, Katy Sowden, Janet E. Burns, Joshua McDermott, Michael P. Krischer, Jeffrey Thornton, John Pareyson, Davide Scherer, Steven S. Shy, Michael E. Reilly, Mary M. Herrmann, David N. Front Neurol Neurology With therapeutic trials on the horizon for Charcot-Marie-Tooth type 1A (CMT1A), reliable, valid, and responsive clinical outcome assessments and biomarkers are essential. Accelerate Clinical Trials in CMT (ACT-CMT) is an international study designed to address important gaps in CMT1A clinical trial readiness including the lack of a validated, responsive functional outcome measure for adults, and a lack of validated biomarkers for multicenter application in clinical trials in CMT1A. The primary aims of ACT-CMT include validation of the Charcot-Marie-Tooth Functional Outcome Measure, magnetic resonance imaging of intramuscular fat accumulation as a lower limb motor biomarker, and in-vivo reflectance confocal microscopy of Meissner corpuscle sensory receptor density, a sensory biomarker. Initial studies have indicated that these measures are feasible, reliable and valid. A large prospective, multi-site study is necessary to fully validate and examine the responsiveness of these outcome measures in relation to existing outcomes for use in future clinical trials involving individuals with CMT1A. Two hundred 15 adults with CMT1A are being recruited to participate in this prospective, international, multi-center study. Serial assessments, up to 3 years, are performed and include the CMT-FOM, CMT Exam Score-Rasch, Overall Neuropathy Limitations Scale, CMT-Health Index, as well as nerve conduction studies, and magnetic resonance imaging and Meissner corpuscle biomarkers. Correlations using baseline data will be examined for validity. Longitudinal analyses will document the changes in function, intramuscular fat accumulation, Meissner corpuscle sensory receptor density. Lastly, we will use anchor-based and other statistical methods to determine the minimally clinically important change for these clinical outcome assessments and biomarkers in CMT1A. Reliable, and responsive clinical outcome assessments of function and disease progression biomarkers are urgently needed for application in early and late phase clinical trials in CMT1A. The ACT-CMT study protocol will address this need through the prospective, longitudinal, multicenter examination in unprecedented detail of novel and existing clinical outcome assessments and motor and sensory biomarkers, and enhance international clinical trial infrastructure, training and preparedness for future therapeutic trials in CMT and related neuropathies. Frontiers Media S.A. 2022-06-27 /pmc/articles/PMC9271780/ /pubmed/35832173 http://dx.doi.org/10.3389/fneur.2022.930435 Text en Copyright © 2022 Eichinger, Sowden, Burns, McDermott, Krischer, Thornton, Pareyson, Scherer, Shy, Reilly and Herrmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Eichinger, Katy
Sowden, Janet E.
Burns, Joshua
McDermott, Michael P.
Krischer, Jeffrey
Thornton, John
Pareyson, Davide
Scherer, Steven S.
Shy, Michael E.
Reilly, Mary M.
Herrmann, David N.
Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A
title Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A
title_full Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A
title_fullStr Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A
title_full_unstemmed Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A
title_short Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A
title_sort accelerate clinical trials in charcot-marie-tooth disease (act-cmt): a protocol to address clinical trial readiness in cmt1a
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271780/
https://www.ncbi.nlm.nih.gov/pubmed/35832173
http://dx.doi.org/10.3389/fneur.2022.930435
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