title: European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.
abstract: In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers.
  
  
  
  All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78.
  
  
  
  All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal.
  
  
  
  EUDRACT 2012-002764-27; Pre-results.
authors.affiliation: Radboud Alzheimer Centre; Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Olga
authors.initials: O
authors.lastname: Meulenbroek
authors.affiliation: Mercer's Institute for Research on Ageing, St James's Hospital, Dublin, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: O'Dwyer
authors.affiliation: Radboud Alzheimer Centre; Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: de Jong
authors.affiliation: Radboud Alzheimer Centre; Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Gerrita
authors.initials: G
authors.lastname: van Spijker
authors.affiliation: Trinity College Dublin (TCD), Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Kennelly
authors.affiliation: Trinity College Dublin (TCD), Dublin, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Cregg
authors.affiliation: Radboud Alzheimer Centre; Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Olde Rikkert
authors.affiliation: Roskamp Institute, Sarasota, Florida, USA.
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.affiliation: Goeteborgs Universitet (UGOT), Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.affiliation: University College Dublin (UCD), Dublin, Ireland.
authors.forename: Cathal
authors.initials: C
authors.lastname: Walsh
authors.affiliation: Mercer's Institute for Research on Ageing, St James's Hospital, Dublin, Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Coen
authors.affiliation: Mercer's Institute for Research on Ageing, St James's Hospital, Dublin, Ireland.
authors.forename: Rose Anne
authors.initials: RA
authors.lastname: Kenny
authors.affiliation: University College Dublin (UCD), Dublin, Ireland.
authors.forename: Leslie
authors.initials: L
authors.lastname: Daly
authors.affiliation: University College Dublin (UCD), Dublin, Ireland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Segurado
authors.affiliation: Goeteborgs Universitet (UGOT), Gothenburg, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Borjesson-Hanson
authors.affiliation: Archer Pharmaceuticals Inc, Sarasota, Florida, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
authors.affiliation: Archer Pharmaceuticals Inc, Sarasota, Florida, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan
authors.affiliation: Department of Laboratory of Geriatric Neuropsychiatry, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" (IRFMN), Milan, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Lucca
authors.affiliation: Department of Laboratory of Geriatric Neuropsychiatry, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" (IRFMN), Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Banzi
authors.affiliation: Centre Hospitalier Regional et Universitaire de Lille (CHRU- LILLE), Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Centre Hospitalier Regional et Universitaire de Lille (CHRU- LILLE), Lille, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Breuilh
authors.affiliation: Universitaet Ulm, (UULM), Ulm, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Riepe
authors.affiliation: Szegedi Tudomanyegyetem (SZEGED), Szeged, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Kalman
authors.affiliation: Centre for Gerontology and Rehabilitation, University College Cork (UCC), Cork, Ireland.
authors.forename: William
authors.identifier: 0000-0001-7370-8630
authors.initials: W
authors.lastname: Molloy
authors.affiliation: Aristotle University of Thessaloniki (AUTH), Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Kings College London (KCL), London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Howard
authors.affiliation: Kings College London (KCL), London, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Adams
authors.affiliation: Molecular Medicine Ireland (MMI), Dublin, Ireland.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Gaynor
authors.affiliation: Mercer's Institute for Research on Ageing, St James's Hospital, Dublin, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Lawlor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002560:Cerebrovascular Circulation; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D000073496:Frailty; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000378:metabolism; D012107:Research Design
chemical_list: D053318:Apolipoprotein E3; D015415:Biomarkers; D002121:Calcium Channel Blockers; D005819:Genetic Markers; D010446:Peptide Fragments; C035100:nilvadipine; D009543:Nifedipine
keywords: GERIATRIC MEDICINE; NEUROLOGY