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

• DOI: 10.1016/j.jalz.2019.06.4956
• Publication Date: 2019-10-24T00:57:57Z
• Authors: Adam L. Boxer; Michael Gold; Howard Feldman; Bradley F. Boeve; Susan L.-J. Dicki...; Howard Fillit; Carole Ho; Robert Paul; Rodney Pearlman; Margaret Sutherland; Ajay Verma; Stephen P. Arneric; Brian M. Alexander; Bradford C. Dicke...; 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
• Keywords: 0301 basic medicine; Aging; LEFFTDS; Clinical Sciences; Clinical Trials and Supportive Activities; 610; ARTFL; Clinical sciences; Neurodegenerative; Frontotemporal lobar degeneration; 03 medical and health sciences; Rare Diseases; Clinical Research; C9orf72; Acquired Cognitive Impairment; MAPT; Humans; Alzheimer's Disease Related Dementias (ADRD); Clinical Trials as Topic; Biomedical and Clinical Sciences; Progressive supranuclear palsy; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); FTD; Biomarker; Congresses as Topic; Magnetic Resonance Imaging; Brain Disorders; 3. Good health; Clinical trial; Frontotemporal Dementia (FTD); Geriatrics; Biological psychology; Dementia; Primary progressive aphasia; Atrophy; Frontotemporal Lobar Degeneration; FTLD; Frontotemporal dementia; GRN; Biomarkers

AbstractIntroductionFrontotemporal 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.MethodsIn 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.ResultsChallenges 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.DiscussionNew 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.