%0 Journal Article
%T Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
%A Agnès Devendeville
%A Ali Sheikhi
%A Anastasia Konsta
%A Anne B？rjesson-Hanson
%A Brian Lawlor
%A Cathal Walsh
%A D. William Molloy
%A Diana G. Taekema
%A Fani Tsolaki-Tagaraki
%A Fiona Crawford
%A Fiona Cregg
%A Flavio Nobili
%A Florence Pasquier
%A Frans R. Verhey
%A Gauthier Calais
%A Giovanni Frisoni
%A Isabelle Lavenu
%A Jessica Adams
%A János Kálmán
%A Laetitia Breuilh
%A Leslie Daly
%A Magda Tsolaki
%A Magdolna Pakaski
%A Marcel G. M. Olde Rikkert
%A Massimo Franceschi
%A Matthias W. Riepe
%A Michael Mullan
%A Olivier Dereeper
%A Olivier Sénéchal
%A Orazio Zanetti
%A Orologas Anastasios
%A Paul Aisen
%A Raffaello Nemni
%A Ricardo Segurado
%A Rita Banzi
%A Robert Coen
%A Robert Howard
%A Rose Anne Kenny
%A Sarah O'Dwyer
%A Sean Kennelly
%A Siobhan Gaynor
%A Styliani Nenopoulou
%A Suzanne Hendrix
%A Ugo Lucca
%A Vincent de la Sayette
%A for the NILVAD Study Group
%J -
%D 2018
%R 10.1371/journal.pmed.1002660
%X Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease.   Methods and findings NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease–specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, ？0.07–1.64) at 13 weeks, 6.41 (5.33–7.49) at 52 weeks, and 9.63 (8.33–10.93) at 78 weeks and on nilvadipine was 0.88 (0.02–1.74) at 13 weeks, 5.75 (4.66–6.85) at 52 weeks, and 9.41 (8.09–10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb
%K Alzheimer's disease
%K Cognitive impairment
%K Blood pressure
%K Calcium antagonist therapy
%K Calcium channels
%K Hypertension
%K Adverse events
%K Blood
%U https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002660