Skip to main content Accessibility help
×
Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-24T05:06:14.109Z Has data issue: false hasContentIssue false

15 - ATRI and ACTC: Academic Programs to Accelerate Alzheimer’s Disease Drug Development

from Section 3 - Alzheimer’s Disease Clinical Trials

Published online by Cambridge University Press:  03 March 2022

Jeffrey Cummings
Affiliation:
University of Nevada, Las Vegas
Jefferson Kinney
Affiliation:
University of Nevada, Las Vegas
Howard Fillit
Affiliation:
Alzheimer’s Drug Discovery Foundation
Get access

Summary

Academic investigators have played key roles in Alzheimer’s disease drug development. This work has been highly collaborative, with innovations in trial design, population characteristics, outcome measures, biomarker utilization and regulatory pathways arising from interactions among academics, industry scientists, regulators, and other stakeholders. The National Institute on Aging (NIA) has funded much of this work, along with the Alzheimer’s Association and other philanthropic organizations. The NIA Alzheimer’s Clinical Trials Consortium (ACTC) supports a nationwide infrastructure to continue academic efforts on trial methodology and the implementation of innovative studies in age-related neurodegenerative disorders. ACTC, with the University of Southern California, Harvard University and the Mayo Clinic, expert trialists from across the country and 35 primary trial sites, conducts a number of multicenter randomized controlled trials. Public-private partnerships are encouraged. Additional innovations include a focus on diversity and inclusion in trial recruitment, involvement of research participants in guiding trial design, and training the next generation of trialists.

Type
Chapter
Information
Alzheimer's Disease Drug Development
Research and Development Ecosystem
, pp. 177 - 189
Publisher: Cambridge University Press
Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Summers, WK, Majovski, LV, Marsh, GM, Tachiki, K, Kling, A. Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. N Engl J Med 1986; 315: 1241–5.Google Scholar
Davis, KL, Thal, LJ, Gamzu, ER, et al. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease. The Tacrine Collaborative Study Group. N Engl J Med 1992; 327: 1253–9.CrossRefGoogle ScholarPubMed
Rosen, WG, Mohs, RC, Davis, KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984; 141: 1356–64.Google Scholar
Thal, LJ. The Alzheimer’s Disease Cooperative Study in 2004. Alzheimer Dis Assoc Disord 2004; 18: 183–5.Google Scholar
Sano, M, Ernesto, C, Thomas, RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997; 336: 1216–22.Google Scholar
Aisen, PS, Schneider, LS, Sano, M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 2008; 300: 1774–83.Google Scholar
Galasko, DR, Peskind, E, Clark, CM, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012; 69: 836–41.Google Scholar
Petersen, RC, Thomas, RG, Grundman, M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005; 352: 2379–88.Google Scholar
Aisen, PS, Davis, KL, Berg, JD, et al. A randomized controlled trial of prednisone in Alzheimer’s disease. Alzheimer’s Disease Cooperative Study. Neurology 2000; 54: 588–93.Google Scholar
Aisen, PS, Schafer, KA, Grundman, M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003; 289: 2819–26.Google Scholar
Mulnard, RA, Cotman, CW, Kawas, C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer’s Disease Cooperative Study. JAMA 2000; 283: 1007–15.Google Scholar
Sano, M, Bell, KL, Galasko, D, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 2011; 77: 556–63.CrossRefGoogle ScholarPubMed
Teri, L, Logsdon, RG, Peskind, E, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology 2000; 55: 1271–8.Google Scholar
Grundman, M, Farlow, M, Peavy, G, et al. A phase I study of AIT-082 in healthy elderly volunteers. J Mol Neurosci 2002; 18: 283–93.Google Scholar
Petersen, RC, Aisen, PS, Beckett, LA, et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology 2010; 74: 201–9.Google Scholar
Weninger, S, Carrillo, MC, Dunn, B, et al. Collaboration for Alzheimer’s Prevention: principles to guide data and sample sharing in preclinical Alzheimer’s disease trials. Alzheimers Dement 2016; 12: 631–2.CrossRefGoogle ScholarPubMed
Vellas, B, Carrillo, MC, Sampaio, C, et al. Designing drug trials for Alzheimer’s disease: what we have learned from the release of the Phase III antibody trials: a report from the EU/US/CTAD Task Force. Alzheimers Dement 2013; 9: 438–44.CrossRefGoogle ScholarPubMed
Sperling, RA, Donohue, MC, Raman, R, et al. Association of factors with elevated amyloid burden in clinically normal older individuals. JAMA Neurol 2020; 77: 735–45.Google Scholar
Sperling, RA, Rentz, DM, Johnson, KA, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med 2014; 6: 228fs13.Google Scholar
Donohue, MC, Sperling, RA, Petersen, R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA 2017; 317: 2305–16.Google Scholar
Donohue, MC, Sperling, RA, Salmon, DP, et al. The Preclinical Alzheimer Cognitive Composite: measuring amyloid-related decline. JAMA Neurol 2014; 71: 961–70.Google Scholar
Siemers, ER, Sundell, KL, Carlson, C, et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement 2016; 12: 110–20.Google Scholar
Doody, RS, Thomas, RG, Farlow, M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 2014; 370: 311–21.Google Scholar
Weiner, MW, Harvey, D, Hayes, J, et al. Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer’s disease in Vietnam Veterans using the Alzheimer’s Disease Neuroimaging Initiative: preliminary report. Alzheimers Dement (N Y) 2017; 3: 177–88.Google Scholar
Craft, S, Raman, R, Chow, TW, et al. Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and alzheimer disease dementia: a randomized clinical trial. JAMA Neurol 2020; 77: 1099–109.Google Scholar
Kaufman, AC, Salazar, SV, Haas, LT, et al. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann Neurol 2015; 77: 953–71.Google Scholar
van Dyck, CH, Nygaard, HB, Chen, K, et al. Effect of AZD0530 on cerebral metabolic decline in Alzheimer disease: a randomized clinical trial. JAMA Neurol 2019; 76: 1219–29.CrossRefGoogle ScholarPubMed
Newhouse, P, Kellar, K, Aisen, P, et al. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology 2012; 78: 91101.Google Scholar
Henley, D, Raghavan, N, Sperling, R, et al. Preliminary results of a trial of atabecestat in preclinical Alzheimer’s disease. N Engl J Med 2019; 380: 1483–5.Google Scholar
Egan, MF, Kost, J, Voss, T, et al. Randomized trial of verubecestat for prodromal Alzheimer’s disease. N Engl J Med 2019; 380: 1408–20.CrossRefGoogle ScholarPubMed
Aisen, PS, Sperling, RA, Cummings, J, et al. The Trial-Ready Cohort for Preclinical/Prodromal Alzheimer’s Disease (TRC-PAD) project: an overview. J Prev Alzheimers Dis 2020; 7: 208–12.Google Scholar
Galasko, D, Bennett, DA, Sano, M, et al. ADCS Prevention Instrument Project: assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials. Alzheimer Dis Assoc Disord 2006; 20: S152–69.Google Scholar
Cummings, JL, Raman, R, Ernstrom, K, Salmon, D, Ferris, SH, Alzheimer’s Disease Cooperative Study Group. ADCS Prevention Instrument Project: behavioral measures in primary prevention trials. Alzheimer Dis Assoc Disord 2006; 20: S147–51.Google Scholar
Schneider, LS, Clark, CM, Doody, R, et al. ADCS Prevention Instrument Project: ADCS-clinicians’ global impression of change scales (ADCS–CGIC), self-rated and study partner-rated versions. Alzheimer Dis Assoc Disord 2006; 20: S124–38.Google Scholar
Ferris, SH, Aisen, PS, Cummings, J, et al. ADCS Prevention Instrument Project: overview and initial results. Alzheimer Dis Assoc Disord 2006; 20: S109–23.Google Scholar
Logsdon, RG, Teri, L, Weiner, MF, et al. Assessment of agitation in Alzheimer’s disease: the agitated behavior in dementia scale. Alzheimer’s Disease Cooperative Study. J Am Geriatr Soc 1999; 47: 1354–8.CrossRefGoogle ScholarPubMed
Morris, JC, Ernesto, C, Schafer, K, et al. Clinical dementia rating training and reliability in multicenter studies: the Alzheimer’s Disease Cooperative Study experience. Neurology 1997; 48: 1508–10.Google Scholar
Schmitt, FA, Ashford, W, Ernesto, C, et al. The severe impairment battery: concurrent validity and the assessment of longitudinal change in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11: S51–6.Google Scholar
Galasko, D, Bennett, D, Sano, M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11: S33–9.Google Scholar
Schneider, LS, Olin, JT, Doody, RS, et al. Validity and reliability of the Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11: S2232.Google Scholar
Ferris, SH, Mackell, JA, Mohs, R, et al. A multicenter evaluation of new treatment efficacy instruments for Alzheimer’s disease clinical trials: overview and general results. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997; 11: S112.Google Scholar
Walsh, SP, Raman, R, Jones, KB, Aisen, PS, Alzheimer’s Disease Cooperative Study Group. ADCS Prevention Instrument Project: the Mail-In Cognitive Function Screening Instrument (MCFSI). Alzheimer Dis Assoc Disord 2006; 20: S170–8.Google Scholar
Amariglio, RE, Donohue, MC, Marshall, GA, et al. Tracking early decline in cognitive function in older individuals at risk for Alzheimer disease dementia: the Alzheimer’s Disease Cooperative Study Cognitive Function Instrument. JAMA Neurol 2015; 72: 446–54.Google Scholar
Aisen, PS, Andrieu, S, Sampaio, C, et al. Report of the task force on designing clinical trials in early (predementia) AD. Neurology 2011; 76: 280–6.Google Scholar
Coley, N, Raman, R, Donohue, MC, et al. Defining the optimal target population for trials of polyunsaturated fatty acid supplementation using the erythrocyte omega-3 index: a step towards personalized prevention of cognitive decline? J Nutr Health Aging 2018; 22: 982–98.Google Scholar
Donohue, MC, Sun, CK, Raman, R, et al. Cross-validation of optimized composites for preclinical Alzheimer’s disease. Alzheimers Dement (N Y) 2017; 3: 123–9.Google ScholarPubMed
Langford, O, Raman, R, Sperling, RA, et al. Predicting amyloid burden to accelerate recruitment of secondary prevention clinical trials. J Prev Alzheimers Dis 2020; 7: 213–18.Google Scholar
Papp, KV, Rentz, DM, Maruff, P, et al. The Computerized Cognitive Composite (C3) in an Alzheimer’s disease secondary prevention trial. J Prev Alzheimers Dis 2021; 8: 5967.Google Scholar
Sano, M, Raman, R, Emond, J, et al. Adding delayed recall to the Alzheimer Disease Assessment Scale is useful in studies of mild cognitive impairment but not Alzheimer disease. Alzheimer Dis Assoc Disord 2011; 25: 122–7.Google Scholar
Li, D, Iddi, S, Thompson, WK, et al. Bayesian latent time joint mixed-effects model of progression in the Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement (Amst) 2018; 10: 657–68.Google ScholarPubMed
Iddi, S, Li, D, Aisen, PS, et al. Estimating the evolution of disease in the Parkinson’s progression markers initiative. Neurodegener Dis 2018; 18: 173–90.Google Scholar
Li, D, Donohue, MC. Disease progression models for dominantly-inherited Alzheimer’s disease. Brain 2018; 141: 1244–6.Google Scholar
Donohue, MC, Jacqmin-Gadda, H, Le Goff, M, et al. Estimating long-term multivariate progression from short-term data. Alzheimers Dement 2014; 10: S400–10.Google Scholar
Donohue, MC, Aisen, PS. Mixed model of repeated measures versus slope models in Alzheimer’s disease clinical trials. J Nutr Health Aging 2012; 16: 360–4.Google Scholar
Donohue, MC, Gamst, AC, Thomas, RG, et al. The relative efficiency of time-to-threshold and rate of change in longitudinal data. Contemp Clin Trials 2011; 32: 685–93.Google Scholar
Li, D, Iddi, S, Aisen, PS, Thompson, WK, Donohue, MC. The relative efficiency of time-to-progression and continuous measures of cognition in presymptomatic Alzheimer’s disease. Alzheimers Dement (N Y) 2019; 5: 308–18.Google Scholar
Nicoll, JA, Wilkinson, D, Holmes, C. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 2003; 9: 448–52.Google Scholar
Satlin, A, Wang, J, Logovinsky, V, et al. Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer’s disease. Alzheimers Dement (N Y) 2016; 2: 112.Google Scholar
Rafii, MS, Zaman, S, Handen, BL. Integrating biomarker outcomes into clinical trials for Alzheimer’s disease in Down syndrome. J Prev Alzheimers Dis 2021; 8: 4851.Google ScholarPubMed
Handen, BL, Lott, IT, Christian, BT, et al. The Alzheimer’s Biomarker Consortium – Down syndrome: rationale and methodology. Alzheimers Dement (Amst) 2020; 12: e12065.Google Scholar
Ovod, V, Ramsey, KN, Mawuenyega, KG, et al. Amyloid beta concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 2017; 13: 841–9.Google Scholar
Nakamura, A, Kaneko, N, Villemagne, VL, et al. High performance plasma amyloid-beta biomarkers for Alzheimer’s disease. Nature 2018; 554: 249–54.Google Scholar
Janelidze, S, Berron, D, Smith, R, et al. Associations of plasma phospho-tau217 levels with tau positron emission tomography in early Alzheimer Disease. JAMA Neurol 2021; 78: 149–56.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×