Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial. 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., Breuilh, L., Daly, L., Hendrix, S., Aisen, P., Gaynor, S., Sheikhi, A., Taekema, D. G., Verhey, F. R., 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., & NILVAD Study Group PLoS medicine, 15(9):e1002660, September, 2018.
doi  abstract   bibtex   
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 \textgreater50 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 \textless27. 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 or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.
@article{lawlor_nilvadipine_2018,
	title = {Nilvadipine in mild to moderate {Alzheimer} disease: {A} randomised controlled trial},
	volume = {15},
	issn = {1549-1676},
	shorttitle = {Nilvadipine in mild to moderate {Alzheimer} disease},
	doi = {10.1371/journal.pmed.1002660},
	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 {\textgreater}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 {\textless}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 or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid.
CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.
TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.},
	language = {eng},
	number = {9},
	journal = {PLoS medicine},
	author = {Lawlor, Brian and Segurado, Ricardo and Kennelly, Sean and Olde Rikkert, Marcel G. M. and Howard, Robert and Pasquier, Florence and Börjesson-Hanson, Anne and Tsolaki, Magda and Lucca, Ugo and Molloy, D. William and Coen, Robert and Riepe, Matthias W. and Kálmán, János and Kenny, Rose Anne and Cregg, Fiona and O'Dwyer, Sarah and Walsh, Cathal and Adams, Jessica and Banzi, Rita and Breuilh, Laetitia and Daly, Leslie and Hendrix, Suzanne and Aisen, Paul and Gaynor, Siobhan and Sheikhi, Ali and Taekema, Diana G. and Verhey, Frans R. and Nemni, Raffaello and Nobili, Flavio and Franceschi, Massimo and Frisoni, Giovanni and Zanetti, Orazio and Konsta, Anastasia and Anastasios, Orologas and Nenopoulou, Styliani and Tsolaki-Tagaraki, Fani and Pakaski, Magdolna and Dereeper, Olivier and de la Sayette, Vincent and Sénéchal, Olivier and Lavenu, Isabelle and Devendeville, Agnès and Calais, Gauthier and Crawford, Fiona and Mullan, Michael and {NILVAD Study Group}},
	month = sep,
	year = {2018},
	pmid = {30248105},
	pmcid = {PMC6152871},
	keywords = {Aged, Alzheimer Disease, Humans, Female, Male, Middle Aged, Disease Progression, Europe, Aged, 80 and over, Treatment Outcome, Double-Blind Method, Nootropic Agents, Calcium Channel Blockers, Cognitive Dysfunction, Nifedipine},
	pages = {e1002660}
}
Downloads: 0
About
Documentation
Keywords
Search
Users
Terms and Conditions of Use
Privacy Policy
Sitemap
© BibBase.org 2021