Display options
Cite
Burns DK, Chiang C, Welsh-Bohmer KA, et al. The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial. Alzheimers Dement (N Y). 2019;5:661-670doi: 10.1016/j.trci.2019.09.010.
Burns, D. K., Chiang, C., Welsh-Bohmer, K. A., Brannan, S. K., Culp, M., O'Neil, J., Runyan, G., Harrigan, P., Plassman, B. L., Lutz, M., Lai, E., Haneline, S., Yarnall, D., Yarbrough, D., Metz, C., Ponduru, S., Sundseth, S., & Saunders, A. M. (2019). The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial. Alzheimer's & dementia (New York, N. Y.), 5661-670. https://doi.org/10.1016/j.trci.2019.09.010
Burns, Daniel K, et al. "The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial." Alzheimer's & dementia (New York, N. Y.) vol. 5 (2019): 661-670. doi: https://doi.org/10.1016/j.trci.2019.09.010
Burns DK, Chiang C, Welsh-Bohmer KA, Brannan SK, Culp M, O'Neil J, Runyan G, Harrigan P, Plassman BL, Lutz M, Lai E, Haneline S, Yarnall D, Yarbrough D, Metz C, Ponduru S, Sundseth S, Saunders AM. The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial. Alzheimers Dement (N Y). 2019 Oct 28;5:661-670. doi: 10.1016/j.trci.2019.09.010. eCollection 2019. PMID: 31720367; PMCID: PMC6838537.
Copy Download .nbib Format: NLM
Share it on

Alzheimers Dement (N Y). 2019 Oct 28;5:661-670. doi: 10.1016/j.trci.2019.09.010. eCollection 2019.

The TOMMORROW study: Design of an Alzheimer's disease delay-of-onset clinical trial.

Alzheimer's & dementia (New York, N. Y.)

Daniel K Burns, Carl Chiang, Kathleen A Welsh-Bohmer, Stephen K Brannan, Meredith Culp, Janet O'Neil, Grant Runyan, Patrick Harrigan, Brenda L Plassman, Michael Lutz, Eric Lai, Stephen Haneline, David Yarnall, Deborah Yarbrough, Craig Metz, Sridevi Ponduru, Scott Sundseth, Ann M Saunders

Affiliations

  1. Zinfandel Pharmaceuticals, Inc., Durham, NC, USA.
  2. Department of Neurology, Bryan Alzheimer's Disease Research Center, Duke University School of Medicine, Durham, NC, USA.
  3. Takeda Development Center Americas, Inc., Deerfield, IL, USA.
  4. Takeda Development Center Americas, Inc., Cambridge, MA, USA.

PMID: 31720367 PMCID: PMC6838537 DOI: 10.1016/j.trci.2019.09.010

Abstract

INTRODUCTION: Alzheimer's disease (AD) is a continuum with neuropathologies manifesting years before clinical symptoms; thus, AD research is attempting to identify more disease-modifying approaches to test treatments administered before full disease expression. Designing such trials in cognitively normal elderly individuals poses unique challenges.

METHODS: The TOMMORROW study was a phase 3 double-blind, parallel-group study designed to support qualification of a novel genetic biomarker risk assignment algorithm (BRAA) and to assess efficacy and safety of low-dose pioglitazone to delay onset of mild cognitive impairment due to AD. Eligible participants were stratified based on the BRAA (using

RESULTS: The focus of this paper is on the design of the study; study results will be presented in a separate paper.

DISCUSSION: The design of the TOMMORROW study addressed many key challenges to conducting a dual-objective phase 3 pivotal AD clinical trial in presymptomatic individuals. Experiences from planning and executing the TOMMORROW study may benefit future AD prevention/delay-of-onset trials.

© 2019 The Authors.

Keywords: Clinical trial design; Delay of onset; Genetic risk for AD; Mild cognitive impairment due to AD; Time to event; Trial population enrichment

References

  1. Neurology. 2008 Sep 30;71(14):1065-71 - PubMed
  2. J Alzheimers Dis. 2011;24(2):363-74 - PubMed
  3. Trends Mol Med. 2008 Feb;14(2):45-53 - PubMed
  4. Exp Neurol. 2011 Jan;227(1):128-35 - PubMed
  5. Med Hypotheses. 2004;63(1):8-20 - PubMed
  6. Dement Geriatr Cogn Disord. 2009;27(5):481-90 - PubMed
  7. Arch Intern Med. 1998 May 11;158(9):1021-31 - PubMed
  8. Neurology. 2011 Sep 27;77(13):1253-62 - PubMed
  9. Mol Neurobiol. 2016 Nov;53(9):6078-6090 - PubMed
  10. Lancet. 2019 Jan 5;393(10166):31-39 - PubMed
  11. Neurology. 2011 Aug 9;77(6):556-63 - PubMed
  12. Alzheimers Dement (N Y). 2018 Sep 06;4:575-590 - PubMed
  13. Alzheimers Dement. 2011 May;7(3):270-9 - PubMed
  14. JAMA. 2016 Nov 15;316(19):1997-2007 - PubMed
  15. Expert Rev Clin Immunol. 2012 Feb;8(2):135-49 - PubMed
  16. Alzheimers Dement (N Y). 2018 May 03;4:195-214 - PubMed
  17. Ann Neurol. 2011 Sep;70(3):418-26 - PubMed
  18. Alzheimers Dement. 2014 Oct;10(5 Suppl):S430-52 - PubMed
  19. Alzheimers Dement (N Y). 2016 Jan 1;2(1):30-44 - PubMed
  20. Neurology. 2009 Dec 15;73(24):2061-70 - PubMed
  21. PLoS One. 2017 Jul 3;12(7):e0180356 - PubMed
  22. Biomark Med. 2012 Aug;6(4):409-17 - PubMed
  23. Am J Geriatr Psychiatry. 2009 Sep;17(9):752-9 - PubMed
  24. JAMA. 2003 May 28;289(20):2651-62 - PubMed
  25. Contemp Clin Trials. 2006 Jun;27(3):238-53 - PubMed
  26. Front Aging Neurosci. 2015 Oct 23;7:199 - PubMed
  27. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8299-302 - PubMed
  28. JAMA. 2010 Nov 3;304(17):1903-11 - PubMed
  29. J Lipid Res. 2005 May;46(5):949-68 - PubMed
  30. Alzheimers Dement. 2013 Jul;9(4):438-44 - PubMed
  31. Alzheimers Dement (N Y). 2018 Jul 14;4:314-323 - PubMed
  32. Alzheimers Dement. 2009 Mar;5(2):93-104 - PubMed
  33. Alzheimers Dement (N Y). 2019 Jun 26;5:254-263 - PubMed
  34. Neurology. 2011 Apr 19;76(16):1389-94 - PubMed
  35. Pharmacogenomics J. 2010 Oct;10(5):375-84 - PubMed
  36. Alzheimers Dement. 2014 Nov;10(6):592-601.e2 - PubMed
  37. Alzheimers Dement (N Y). 2017 Sep 06;3(4):524-530 - PubMed
  38. Clin Pharmacol Ther. 2013 Feb;93(2):177-85 - PubMed
  39. Alzheimers Dement. 2011 May;7(3):263-9 - PubMed
  40. Curr Alzheimer Res. 2011 Aug;8(5):592-606 - PubMed
  41. J Intern Med. 2014 Mar;275(3):251-83 - PubMed
  42. J Neuropathol Exp Neurol. 1994 Sep;53(5):429-37 - PubMed
  43. Cell. 2013 Apr 25;153(3):707-20 - PubMed
  44. Am J Geriatr Psychiatry. 2005 Nov;13(11):950-8 - PubMed
  45. Alzheimers Dement. 2011 May;7(3):280-92 - PubMed

Publication Types