Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial
S M Mills, J Mallmann, A M Santacruz, A Fuqua, M Carril, P S Aisen, M C Althage, S Belyew, T L Benzinger, W S Brooks, V D Buckles, N J Cairns, D Clifford, A Danek, A M Fagan, M Farlow, N Fox, B Ghetti, A M Goate, D Heinrichs, R Hornbeck, C Jack, M Jucker, W E Klunk, D S Marcus, R N Martins, C M Masters, R Mayeux, E McDade, J C Morris, A Oliver, J M Ringman, M N Rossor, S Salloway, P R Schofield, J Snider, P Snyder, R A Sperling, C Stewart, R G Thomas, C Xiong, R J Bateman, S M Mills, J Mallmann, A M Santacruz, A Fuqua, M Carril, P S Aisen, M C Althage, S Belyew, T L Benzinger, W S Brooks, V D Buckles, N J Cairns, D Clifford, A Danek, A M Fagan, M Farlow, N Fox, B Ghetti, A M Goate, D Heinrichs, R Hornbeck, C Jack, M Jucker, W E Klunk, D S Marcus, R N Martins, C M Masters, R Mayeux, E McDade, J C Morris, A Oliver, J M Ringman, M N Rossor, S Salloway, P R Schofield, J Snider, P Snyder, R A Sperling, C Stewart, R G Thomas, C Xiong, R J Bateman
Abstract
The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to direct the design and management of interventional therapeutic trials of international DIAN and autosomal dominant Alzheimer's disease (ADAD) participants. The goal of the DIAN-TU is to implement safe trials that have the highest likelihood of success while advancing scientific understanding of these diseases and clinical effects of proposed therapies. The DIAN-TU has launched a trial design that leverages the existing infrastructure of the ongoing DIAN observational study, takes advantage of a variety of drug targets, incorporates the latest results of biomarker and cognitive data collected during the observational study, and implements biomarkers measuring Alzheimer's disease (AD) biological processes to improve the efficiency of trial design. The DIAN-TU trial design is unique due to the sophisticated design of multiple drugs, multiple pharmaceutical partners, academics servings as sponsor, geographic distribution of a rare population and intensive safety and biomarker assessments. The implementation of the operational aspects such as home health research delivery, safety magnetic resonance imagings (MRIs) at remote locations, monitoring clinical and cognitive measures, and regulatory management involving multiple pharmaceutical sponsors of the complex DIAN-TU trial are described.
Keywords: Alzheimer's disease; Amyloid deposition; Amyloid-beta (Aβ); Autosomal dominant; Autosomique dominante; Bêta-amyloïde; Clinical trial; Dépôt de substance amyloïde; Essai clinique; Maladie d’Alzheimer.
Conflict of interest statement
Disclosure of interests
R.J.B. has consulted for Pfizer, DZNE, Probiodrug AG, Medscape, En Vivo (SAB) and has research grants with AstraZeneca, Merck and Eli Lilly in the past year. Washington University and R.J.B. have a financial interest in C2 N Diagnostics, which uses the SILK methodology in human studies. R.J.B. is a co-inventor on U.S. patent 7,892,845 “Methods for measuring the metabolism of neurally derived biomolecules in vivo.” Washington University, with R.J.B. are co-inventors, has also submitted the U.S. non-provisional patent application “Methods for measuring the metabolism of CNS derived biomolecules in vivo,” serial #12/267,974. R.J.B. is co-inventor on U.S. Provisional Application 61/728,692 “Methods of diagnosing amyloid pathologies using analysis of amyloid-beta enrichment kinetics”.
D.M.C. has consulted for Pfizer, Genzyme, Millennium, PML Consortium, Amgen, Quintiles, Arnold Todara & Welch, W. Holt Smith Attorney, Biogen Idec, Cytheris, FDA hearing, Genentech, GSK and has research grants with Bavarian Nordic, Lilly, Roche and Biogen Idec.
Published by Elsevier Masson SAS.
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Source: PubMed