New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures

Adam L. Boxer; Michael Gold; Howard Feldman; Bradley F. Boeve; Susan L.J. Dickinson; Howard Fillit; Carole Ho; Robert Paul; Rodney Pearlman; Margaret Sutherland; Ajay Verma; Stephen P. Arneric; Brian M. Alexander; Bradford C. Dickerson; Earl Ray Dorsey; Murray Grossman; Edward D. Huey; Michael C. Irizarry; William J. Marks; Mario Masellis; Frances McFarland; Debra Niehoff; Chiadi U. Onyike; Sabrina Paganoni; Michael A. Panzara; Kenneth Rockwood; Jonathan D. Rohrer; Howard Rosen; Robert N. Schuck; Holly D. Soares; Nadine Tatton

doi:10.1016/j.jalz.2019.06.4956

New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures

Adam L. Boxer, Michael Gold, Howard Feldman, Bradley F. Boeve, Susan L.J. Dickinson, Howard Fillit, Carole Ho, Robert Paul, Rodney Pearlman, Margaret Sutherland, Ajay Verma, Stephen P. Arneric, Brian M. Alexander, Bradford C. Dickerson, Earl Ray Dorsey, Murray Grossman, Edward D. Huey, Michael C. Irizarry, William J. Marks, Mario MasellisFrances McFarland, Debra Niehoff, Chiadi U. Onyike, Sabrina Paganoni, Michael A. Panzara, Kenneth Rockwood, Jonathan D. Rohrer, Howard Rosen, Robert N. Schuck, Holly D. Soares, Nadine Tatton

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

47 Citations (Scopus)

Abstract

Introduction: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. Methods: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. Results: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. Discussion: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.

Original language	English
Pages (from-to)	131-143
Number of pages	13
Journal	Alzheimer's and Dementia
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/j.jalz.2019.06.4956
Publication status	Published - Jan 1 2020

Bibliographical note

Funding Information:
This work was funded by the Association for Frontotemporal Degeneration and the NIH (U54NS092089, R01AG038791, U01AG045390). A.L.B. received research support from the NIH (U54NS092089, R01AG038791, U01AG045390), the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation and the Alzheimer's Association.

Funding Information:
This work was funded by the Association for Frontotemporal Degeneration and the NIH ( U54NS092089 , R01AG038791 , U01AG045390 ).

Publisher Copyright:
© 2019 the Alzheimer's Association

ASJC Scopus Subject Areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jalz.2019.06.4956

Cite this

Boxer, A. L., Gold, M., Feldman, H., Boeve, B. F., Dickinson, S. L. J., Fillit, H., Ho, C., Paul, R., Pearlman, R., Sutherland, M., Verma, A., Arneric, S. P., Alexander, B. M., Dickerson, B. C., Dorsey, E. R., Grossman, M., Huey, E. D., Irizarry, M. C., Marks, W. J., ... Tatton, N. (2020). New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures. Alzheimer's and Dementia, 16(1), 131-143. https://doi.org/10.1016/j.jalz.2019.06.4956

Boxer, AL, Gold, M, Feldman, H, Boeve, BF, Dickinson, SLJ, Fillit, H, Ho, C, Paul, R, Pearlman, R, Sutherland, M, Verma, A, Arneric, SP, Alexander, BM, Dickerson, BC, Dorsey, ER, Grossman, M, Huey, ED, Irizarry, MC, Marks, WJ, Masellis, M, McFarland, F, Niehoff, D, Onyike, CU, Paganoni, S, Panzara, MA, Rockwood, K, Rohrer, JD, Rosen, H, Schuck, RN, Soares, HD & Tatton, N 2020, 'New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures', Alzheimer's and Dementia, vol. 16, no. 1, pp. 131-143. https://doi.org/10.1016/j.jalz.2019.06.4956

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title = "New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures",

abstract = "Introduction: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. Methods: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. Results: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. Discussion: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.",

author = "Boxer, {Adam L.} and Michael Gold and Howard Feldman and Boeve, {Bradley F.} and Dickinson, {Susan L.J.} and Howard Fillit and Carole Ho and Robert Paul and Rodney Pearlman and Margaret Sutherland and Ajay Verma and Arneric, {Stephen P.} and Alexander, {Brian M.} and Dickerson, {Bradford C.} and Dorsey, {Earl Ray} and Murray Grossman and Huey, {Edward D.} and Irizarry, {Michael C.} and Marks, {William J.} and Mario Masellis and Frances McFarland and Debra Niehoff and Onyike, {Chiadi U.} and Sabrina Paganoni and Panzara, {Michael A.} and Kenneth Rockwood and Rohrer, {Jonathan D.} and Howard Rosen and Schuck, {Robert N.} and Soares, {Holly D.} and Nadine Tatton",

note = "Funding Information: This work was funded by the Association for Frontotemporal Degeneration and the NIH (U54NS092089, R01AG038791, U01AG045390). A.L.B. received research support from the NIH (U54NS092089, R01AG038791, U01AG045390), the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation and the Alzheimer's Association. Funding Information: This work was funded by the Association for Frontotemporal Degeneration and the NIH ( U54NS092089 , R01AG038791 , U01AG045390 ). Publisher Copyright: {\textcopyright} 2019 the Alzheimer's Association",

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T1 - New directions in clinical trials for frontotemporal lobar degeneration

T2 - Methods and outcome measures

AU - Boxer, Adam L.

AU - Gold, Michael

AU - Feldman, Howard

AU - Boeve, Bradley F.

AU - Dickinson, Susan L.J.

AU - Fillit, Howard

AU - Ho, Carole

AU - Paul, Robert

AU - Pearlman, Rodney

AU - Sutherland, Margaret

AU - Verma, Ajay

AU - Arneric, Stephen P.

AU - Alexander, Brian M.

AU - Dickerson, Bradford C.

AU - Dorsey, Earl Ray

AU - Grossman, Murray

AU - Huey, Edward D.

AU - Irizarry, Michael C.

AU - Marks, William J.

AU - Masellis, Mario

AU - McFarland, Frances

AU - Niehoff, Debra

AU - Onyike, Chiadi U.

AU - Paganoni, Sabrina

AU - Panzara, Michael A.

AU - Rockwood, Kenneth

AU - Rohrer, Jonathan D.

AU - Rosen, Howard

AU - Schuck, Robert N.

AU - Soares, Holly D.

AU - Tatton, Nadine

N1 - Funding Information: This work was funded by the Association for Frontotemporal Degeneration and the NIH (U54NS092089, R01AG038791, U01AG045390). A.L.B. received research support from the NIH (U54NS092089, R01AG038791, U01AG045390), the Tau Research Consortium, the Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Corticobasal Degeneration Solutions, the Alzheimer's Drug Discovery Foundation and the Alzheimer's Association. Funding Information: This work was funded by the Association for Frontotemporal Degeneration and the NIH ( U54NS092089 , R01AG038791 , U01AG045390 ). Publisher Copyright: © 2019 the Alzheimer's Association

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Introduction: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. Methods: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. Results: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. Discussion: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.

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New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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