A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes).
Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52.
Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo.
Frontiers in Neuroscience, Editorial Board, 2008-present. Aging, Neuropsychology and Cognition, Editorial Board, 2006-present.
Support for clinical research to Georgetown University from Biogen Idec, Lilly, Merck, Toyama and Transition Therapeutics, 2013-present.
NIA U01 AG10483, Project PI and Member of Steering Committee, 2006- present.
(1) Journal of Prevention of Alzheimers Disease (associate editor), 2015 (2) Alzheimer?s & Dementia: Translational Research & Clinical Interventions (editorial board), 2015
(1) Consulted with DIAN Trial unit. (2) Consulted with Alzheimer Prevention Initiative
Funded as Core Director by NIH/NIA grant #AG10483 (2012-Present) Funded as Biostatistican by NIH/NIA grant #AG024904 (2010-Present)
(1) Elan Pharmaceuticals (2) Pfizer Inc (3) GlaxoSmithKline (4) Bristol-Myers Squibb (5) AbbVie Inc (6) Roche Pharmaceuticals
(1) Bristol-Myers Squibb, funding for travel to speak at conference
(1) Amy Arnsten, PhD (wife) ?Use of guanfacine in the treatment of behavioral disorders?, issued 1998. (2) Amy Arnsten, PhD (wife) ?Use of lofexidine in the treatment of behavioral disorders?, issued 1999.
(1) Amy Arnsten, PhD (wife), receives royalties for: The Neuropharmacology of Stimulant Drugs: Implications for AD/HD. M. Solanto, A. Arnsten and F.X. Castellanos, eds., Oxford University Press, New York, NY, 2000.
(1) Elan Pharmaceuticals (2) Pfizer Inc (3) GlaxoSmithKline (4) Bristol-Myers Squibb (5) AbbVie Inc (6) Roche Pharmaceuticals
(1) Merck & Co. Inc. (2) Toyama Chemical Co., Ltd. (3) Forum Pharmaceuticals (4) TauRx (5) Eli Lilly and Company (6) Pfizer, Inc. (7) Roche Pharmaceuticals (8) Eisai, Inc (9) Biogen Idec (10) Genentech, Inc (11) Wyeth Research (12) Bristol-Myers Squibb Company (13) Elan Pharmaceuticals (14) Baxter Pharmaceuticals (15) Janssen Pharmaceuticals
(1) NIH/NIA, 1 P50 AG047270-01, Investigator, 2015-2020 (2) NIH/NCATS, 4UH3TR000967-02, Co-Principal Investigator, 2013-2016 (3) NIH/NINDS, 1-R01-NS087568, Investigator, 2014-2019 (4) NIH/NIA, 1-RO1-AG046543, Investigator, 2014-2019 (5) NIH/NIA, 1-R01-AG034953-01, Investigator, 2010-2014 (6) NIH/NIA, 2-U01AG024904-06, Site Investigator, 2010-2015 (7) NIH/NIA, 7-RF1-AG041845-02, Site Investigator, 2014-2016 (8) NIH/NIA, 2-U19-AG10483, Site Investigator, 2012-2017 (9) NIH/NIA, 1-R01-AG030457-01A1, Principal Investigator, 2008-2012
(1) Amy Arnsten, PhD (wife), owned a patent ?Use of guanfacine in the treatment of behavioral disorders? (issued 1998) that was licensed to Shire Pharmaceuticals for the use of guanfacine as a treatment for Attention Deficit Hyperactivity Disorder (ADHD). She has royalty payments from Shire Pharmaceuticals.
(3)Genentech, grant recipient (4)Merck, grant recipient (5)Takeda, grant recipient (6)Transition Therapeutics, grant recipient (7) Grifols, grant recipient (8) Pfizer, grant recipient
(1)National Institute on Aging, grant recipient (2) Alzheimer's Disease Cooperative Study, Steering Committee Member (3) ADNI, Steering Committee Member
Human Longevity Inc., Scientific Advisory Board Eli Lilly Pharmaceuticals Biomarker Business Unit Advisory Board Avanir Pharmacueticals Advisory Board Novartis Pharmaceuticals Advisory Board Genentech Advisory Board
Eli Lilly, Avanir, Novartis, Genentech, Roche, CorTechs Labs
Janssen Alzheimer Immunotherapy General Electric Navidea Toyama Eli Lilly Pharmaceuticals
NIA R01AG034062, PI, 2011-2015 NIH K02067427 (NS 067427), PI, 2010-2014 NIH 2P50AG005131-266214, Co-Investigator, 2010-2014 NIH U01 AG10483, Imaging Core Director, 2010-2015 NIH 1RC2AG036535, Site PI, 2010-2013
Cortechs Labs, 2010-2015 Human Longevity Inc., 2015
Editorial Boards: BMC Medicine, Alzheimer's Research & Therapy, Journal of Prevention of Alzheimer's Disease
DHA therapy for apolipoprotein E4 negative ALzheimer's Disease; any potential royalties assigned in full to UCSD.
Elan Corporation, consultant, 2008-10 Wyeth, consultant, 2008-10 Eisai Inc., consultant, 2008-10 Schering-Plough Corp., consultant, 2008-10 Bristol-Myers Squibb, consultant, 2008-10 Eli Lilly and Company, consultant (unpaid), 2008-10 Merck & Co., consultant, 2008-10 Roche, consultant, 2008-11 Amgen, consultant, 2008-10 Genentech, Inc., 2009-2010 Abbott, consultant, 2008-10 Pfizer Inc, consultant (unpaid), 2008-10 Novartis, consultant, 2008-11 Bayer, consultant, 2009-10 Medivation, Inc., consultant, 2008-10 Daiichi Sankyo, consultant, 2010 Astellas, consultant, 2010 Dainippon, consultant, 2010 Biomarin, consultant, 2010 Solvay, consultant, 2010 Ostuka, consultant, 2010 AstraZeneca, consultant, 2010 Janssen, consultant, 2010
NIA U01-AG10483 (PI), NIA U01-AG024904 (Coordinating Center Director), NIA R01-AG030048 (PI), and R01-AG16381 (Co-I)]
Coinvestigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by NIH.
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