INTREPAD: a randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease

Objective: Evaluate the safety and efficacy of low-dose naproxen for prevention of progression in pre-symptomatic AD among cognitively intact persons at-risk.
Methods: INTREPAD, a two-year double-masked pharmaco-prevention trial, enrolled 195 AD family history-positive elderly (mean age 63 years) screened carefully to exclude cognitive disorder. These were randomized 1:1 to naproxen sodium 220mg 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 pre-symptomatic Alzheimer Progression Score (APS).
Results: Safety: Naproxen-treated individuals showed a clear excess of adverse events. Efficacy: Among treatment groups combined, the APS increased by 0.101 points/year (S.E = 0.014; P <...