TY - JOUR
T1 - A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease
AU - PREVENT-AD Research Group
AU - Meyer, Pierre François
AU - Tremblay-Mercier, Jennifer
AU - Leoutsakos, Jeannie
AU - Madjar, Cécile
AU - Lafaille-Maignan, Marie Élyse
AU - Savard, Melissa
AU - Rosa-Neto, Pedro
AU - Poirier, Judes
AU - Etienne, Pierre
AU - Breitner, John
N1 - Funding Information:
This trial was supported by McGill University, by an unrestricted gift from Pfizer Canada, and by infrastructure support from the Canada Fund for Innovation. Dr. Breitner’s efforts were supported by a Canada Research Chair award from the government of Canada. Genetic and laboratory work (J.P.) were supported by the Fonds de Recherche du Québec–Santé (FRQ-S) and the J.L. Levesque Foundation. P.-F.M. is supported by funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative. M.-E.L.-M. and P.-F.M. received research support from the Lazlo & Etelka Kollar fellowship fund for this project. Additional support was provided by the Douglas Mental Health University Institute Foundation. The funding agencies had no role in study design, data analysis, or interpretation of results.
Funding Information:
The Article Processing Charge was funded by the Fonds de Recherche du Québec-Santé.
Publisher Copyright:
Copyright © 2019 The Author(s).
PY - 2019/4/30
Y1 - 2019/4/30
N2 - Objective To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk. Methods Investigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer’s Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history–positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in;50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS). Results Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p < 10−12), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64–1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD. Conclusions In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD. Classification of evidence This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD.
AB - Objective To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk. Methods Investigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer’s Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history–positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in;50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS). Results Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p < 10−12), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64–1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD. Conclusions In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD. Classification of evidence This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD.
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M3 - Article
C2 - 30952794
AN - SCOPUS:85065508203
SN - 0028-3878
VL - 92
SP - E2070-E2080
JO - Neurology
JF - Neurology
IS - 18
ER -