Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

Brian Lawlor; Ricardo Segurado; Sean Kennelly; Marcel G M Olde Rikkert; Robert Howard; Florence Pasquier; Anne Börjesson-Hanson; Magda Tsolaki; Ugo Lucca; D William Molloy; Robert Coen; Matthias W Riepe; János Kálmán; Rose Anne Kenny; Fiona Cregg; Sarah O'Dwyer; Cathal Walsh; Jessica Adams; Rita Banzi; Laetitia Breuilh; Leslie Daly; Suzanne Hendrix; Paul Aisen; Siobhan Gaynor; Ali Sheikhi; Diana G Taekema; Frans R Verhey; Raffaello Nemni; Flavio Nobili; Massimo Franceschi; Giovanni Frisoni; Orazio Zanetti; Anastasia Konsta; Orologas Anastasios; Styliani Nenopoulou; Fani Tsolaki-Tagaraki; Magdolna Pakaski; Olivier Dereeper; Vincent de la Sayette; Olivier Sénéchal; Isabelle Lavenu; Agnès Devendeville; Gauthier Calais; Fiona Crawford; Michael Mullan; NILVAD Study Group

doi:10.1371/journal.pmed.1002660

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

Brian Lawlor, Ricardo Segurado, Sean Kennelly, Marcel G M Olde Rikkert, Robert Howard, Florence Pasquier, Anne Börjesson-Hanson, Magda Tsolaki, Ugo Lucca, D William Molloy, Robert Coen, Matthias W Riepe, János Kálmán, Rose Anne Kenny, Fiona Cregg, Sarah O'Dwyer, Cathal Walsh, Jessica Adams, Rita Banzi, Laetitia BreuilhLeslie Daly, Suzanne Hendrix, Paul Aisen, Siobhan Gaynor, Ali Sheikhi, Diana G Taekema, Frans R Verhey, Raffaello Nemni, Flavio Nobili, Massimo Franceschi, Giovanni Frisoni, Orazio Zanetti, Anastasia Konsta, Orologas Anastasios, Styliani Nenopoulou, Fani Tsolaki-Tagaraki, Magdolna Pakaski, Olivier Dereeper, Vincent de la Sayette, Olivier Sénéchal, Isabelle Lavenu, Agnès Devendeville, Gauthier Calais, Fiona Crawford, Michael Mullan, NILVAD Study Group

Research output: Contribution to journal › Article › peer-review

Abstract

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

Original language	English
Pages (from-to)	e1002660
Journal	PLoS Medicine
Volume	15
Issue number	9
DOIs	https://doi.org/10.1371/journal.pmed.1002660
Publication status	Published - Sep 2018

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Lawlor, B., Segurado, R., Kennelly, S., Olde Rikkert, M. G. M., Howard, R., Pasquier, F., Börjesson-Hanson, A., Tsolaki, M., Lucca, U., Molloy, D. W., Coen, R., Riepe, M. W., Kálmán, J., Kenny, R. A., Cregg, F., O'Dwyer, S., Walsh, C., Adams, J., Banzi, R., ... Group, NILVAD. S. (2018). Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial. PLoS Medicine, 15(9), e1002660. https://doi.org/10.1371/journal.pmed.1002660

Nilvadipine in mild to moderate Alzheimer disease : A randomised controlled trial. / Lawlor, Brian; Segurado, Ricardo; Kennelly, Sean; Olde Rikkert, Marcel G M; Howard, Robert; Pasquier, Florence; Börjesson-Hanson, Anne; Tsolaki, Magda; Lucca, Ugo; Molloy, D William; Coen, Robert; Riepe, Matthias W; Kálmán, János; Kenny, Rose Anne; Cregg, Fiona; O'Dwyer, Sarah; Walsh, Cathal; Adams, Jessica; Banzi, Rita; Breuilh, Laetitia; Daly, Leslie; Hendrix, Suzanne; Aisen, Paul; Gaynor, Siobhan; Sheikhi, Ali; Taekema, Diana G; Verhey, Frans R; Nemni, Raffaello; Nobili, Flavio; Franceschi, Massimo; Frisoni, Giovanni; Zanetti, Orazio; Konsta, Anastasia; Anastasios, Orologas; Nenopoulou, Styliani; Tsolaki-Tagaraki, Fani; Pakaski, Magdolna; Dereeper, Olivier; de la Sayette, Vincent; Sénéchal, Olivier; Lavenu, Isabelle; Devendeville, Agnès; Calais, Gauthier; Crawford, Fiona; Mullan, Michael; Group, NILVAD Study.

In: PLoS Medicine, Vol. 15, No. 9, 09.2018, p. e1002660.

Research output: Contribution to journal › Article › peer-review

Lawlor, B, Segurado, R, Kennelly, S, Olde Rikkert, MGM, Howard, R, Pasquier, F, Börjesson-Hanson, A, Tsolaki, M, Lucca, U, Molloy, DW, Coen, R, Riepe, MW, Kálmán, J, Kenny, RA, Cregg, F, O'Dwyer, S, Walsh, C, Adams, J, Banzi, R, Breuilh, L, Daly, L, Hendrix, S, Aisen, P, Gaynor, S, Sheikhi, A, Taekema, DG, Verhey, FR, Nemni, R, Nobili, F, Franceschi, M, Frisoni, G, Zanetti, O, Konsta, A, Anastasios, O, Nenopoulou, S, Tsolaki-Tagaraki, F, Pakaski, M, Dereeper, O, de la Sayette, V, Sénéchal, O, Lavenu, I, Devendeville, A, Calais, G, Crawford, F, Mullan, M & Group, NILVADS 2018, 'Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.', PLoS Medicine, vol. 15, no. 9, pp. e1002660. https://doi.org/10.1371/journal.pmed.1002660

Lawlor, Brian ; Segurado, Ricardo ; Kennelly, Sean ; Olde Rikkert, Marcel G M ; Howard, Robert ; Pasquier, Florence ; Börjesson-Hanson, Anne ; Tsolaki, Magda ; Lucca, Ugo ; Molloy, D William ; Coen, Robert ; Riepe, Matthias W ; Kálmán, János ; Kenny, Rose Anne ; Cregg, Fiona ; O'Dwyer, Sarah ; Walsh, Cathal ; Adams, Jessica ; Banzi, Rita ; Breuilh, Laetitia ; Daly, Leslie ; Hendrix, Suzanne ; Aisen, Paul ; Gaynor, Siobhan ; Sheikhi, Ali ; Taekema, Diana G ; Verhey, Frans R ; Nemni, Raffaello ; Nobili, Flavio ; Franceschi, Massimo ; Frisoni, Giovanni ; Zanetti, Orazio ; Konsta, Anastasia ; Anastasios, Orologas ; Nenopoulou, Styliani ; Tsolaki-Tagaraki, Fani ; Pakaski, Magdolna ; Dereeper, Olivier ; de la Sayette, Vincent ; Sénéchal, Olivier ; Lavenu, Isabelle ; Devendeville, Agnès ; Calais, Gauthier ; Crawford, Fiona ; Mullan, Michael ; Group, NILVAD Study. / Nilvadipine in mild to moderate Alzheimer disease : A randomised controlled trial. In: PLoS Medicine. 2018 ; Vol. 15, No. 9. pp. e1002660.

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title = "Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.",

abstract = "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 ",

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T1 - Nilvadipine in mild to moderate Alzheimer disease

T2 - A randomised controlled trial.

AU - Lawlor, Brian

AU - Segurado, Ricardo

AU - Kennelly, Sean

AU - Olde Rikkert, Marcel G M

AU - Howard, Robert

AU - Pasquier, Florence

AU - Börjesson-Hanson, Anne

AU - Tsolaki, Magda

AU - Lucca, Ugo

AU - Molloy, D William

AU - Coen, Robert

AU - Riepe, Matthias W

AU - Kálmán, János

AU - Kenny, Rose Anne

AU - Cregg, Fiona

AU - O'Dwyer, Sarah

AU - Walsh, Cathal

AU - Adams, Jessica

AU - Banzi, Rita

AU - Breuilh, Laetitia

AU - Daly, Leslie

AU - Hendrix, Suzanne

AU - Aisen, Paul

AU - Gaynor, Siobhan

AU - Sheikhi, Ali

AU - Taekema, Diana G

AU - Verhey, Frans R

AU - Nemni, Raffaello

AU - Nobili, Flavio

AU - Franceschi, Massimo

AU - Frisoni, Giovanni

AU - Zanetti, Orazio

AU - Konsta, Anastasia

AU - Anastasios, Orologas

AU - Nenopoulou, Styliani

AU - Tsolaki-Tagaraki, Fani

AU - Pakaski, Magdolna

AU - Dereeper, Olivier

AU - de la Sayette, Vincent

AU - Sénéchal, Olivier

AU - Lavenu, Isabelle

AU - Devendeville, Agnès

AU - Calais, Gauthier

AU - Crawford, Fiona

AU - Mullan, Michael

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PY - 2018/9

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N2 - 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

AB - 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

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DO - 10.1371/journal.pmed.1002660

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SP - e1002660

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