A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study

Abstract

Introduction: This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild-to-moderate Alzheimer's disease (AD). Methods: Three hundred forty-seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6-week period of weekly conventional PE followed by a 12-month period of monthly low-volume PE), and placebo (sham). Results: PE-treated patients performed significantly better than placebo for the co-primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL; P =.03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog; P =.06; 66% less decline) scores at month 14. Moderate-AD patients (baseline Mini-Mental State Examination [MMSE] 18-21) scored better on ADCS-ADL (P =.002) and ADAS-Cog (P =.05), 61% less decline both. There were no changes in mild-AD patients (MMSE 22-26). PE-treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (P =.002; 71% less decline) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) (P