TY - JOUR
T1 - Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials
AU - Goldman, Jennifer G.
AU - Forsberg, Leah K.
AU - Boeve, Bradley F.
AU - Armstrong, Melissa J.
AU - Irwin, David J.
AU - Ferman, Tanis J.
AU - Galasko, Doug
AU - Galvin, James E.
AU - Kaufer, Daniel
AU - Leverenz, James
AU - Lippa, Carol F.
AU - Marder, Karen
AU - Abler, Victor
AU - Biglan, Kevin
AU - Irizarry, Michael
AU - Keller, Bill
AU - Munsie, Leanne
AU - Nakagawa, Masaki
AU - Taylor, Angela
AU - Graham, Todd
N1 - Funding Information:
Armstrong—Dr. Armstrong has received grant/research funding from AHRQ (K08HS24159), NIA P30AG047266, and the Florida Department of Health (grant 20A08) and compensation from the AAN for work as an evidence-based medicine methodology consultant and is on the level of evidence editorial board for Neurology® and related publications (uncompensated).
Funding Information:
Galasko—Dr. Galasko has received grant/research funding from NIH/NIA, State of California, and Michael J Fox Foundation and serves as a consultant to Esai, Biogen, Fujirebio, Amprion, vTv Pharmaceuticals, and DSMB for Cognition Therapeutics.
Funding Information:
Boeve—Dr. Boeve has received grant/research funding from the NIH (AG016574, AG062677, NS100620, AG056639, AG054256, AG050326), the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, and the Little Family Foundation and serves as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma; Scientific Advisory Board of the Tau Consortium.
Funding Information:
Goldman—Dr. Goldman has received grant/research funding from Michael J. Fox Foundation and Parkinson’s Foundation, served as consultant for Worldwide Med, and has received honoraria from Davis Phinney Foundation, International Parkinson and Movement Disorder Society, and Parkinson’s Foundation.
Funding Information:
The IAC meeting was supported by the LBDA. Acknowledgements
Funding Information:
We would like to dedicate this manuscript in memory of Daniel I. Kaufer, MD, member of the LBDA Scientific Advisory Council, and Research Centers of Excellence, for his contributions to the LBDA Industry Advisory Council and the field. Dr. Kaufer served as Associate Professor of Neurology and Psychiatry; the Division Chief, Cognitive Neurology and Memory Disorders; the founding Director of the UNC Memory Disorders Program; and Co-director of the Carolina Alzheimer?s Network. He passed away on July 2, 2020, after a brief illness. Dr. Kaufer is remembered for his clinical care and research in LBD and frontotemporal degeneration, contributions to the development of important clinical assessment tools, and compassion for his patients and family caregivers. We thank Nina Silverberg, PhD, for the thoughtful discussion on topics covered in this manuscript.
Funding Information:
Marder—Dr. Marder has received grant/research funding from NIH (U01NS100600, U24NA107168, UL1TR001873, R01NS0736 71, R01LM00986, R01NS-9435, RM1HG007257), Michael J. Fox Foundation, Parkinson’s Foundation, CHDI, and Huntington's Disease Society of America.
Funding Information:
Irwin—Dr. Irwin has received grant/research funding from NIH NS109260, U01-NS100610, R01-AG056014, P30-AG010124, U19-AG062418, and Penn Institute on Aging.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson’s disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.
AB - Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson’s disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.
KW - Biomarker
KW - Clinical trial readiness
KW - Dementia
KW - Lewy bodies
KW - Neuropsychology
KW - Outcome measure
KW - Parkinsonism
KW - Parkinson’s disease
KW - Primary endpoint
KW - Randomized controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85094629709&partnerID=8YFLogxK
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U2 - 10.1186/s13195-020-00703-5
DO - 10.1186/s13195-020-00703-5
M3 - Review article
C2 - 33121510
AN - SCOPUS:85094629709
SN - 1758-9193
VL - 12
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 137
ER -