A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study.
Level 2 - randomized trial
Phase 2b/3 multicenter randomized sham-controlled trial
PubMed 32715623 · doi:10.1002/alz.12137
What was done
In the multicenter AMBAR phase 2b/3 trial, 347 patients with mild-to-moderate Alzheimer's disease (out of 496 screened) were randomized (1:1:1:1) into three plasma exchange (PE) regimens with varying doses of albumin and intravenous immunoglobulin replacement, or sham placebo. The protocol consisted of 6 weeks of weekly conventional PE followed by 12 months of monthly low-volume PE. Co-primary endpoints were changes from baseline to month 14 in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).
What was found
At 14 months, PE-treated patients demonstrated 52% less decline on the ADCS-ADL (P = .03) and a trend of 66% less decline on the ADAS-Cog (P = .06) versus placebo. In moderate AD (baseline MMSE 18-21), PE-treated patients had 61% less decline on both ADCS-ADL (P = .002) and ADAS-Cog (P = .05); no significant changes occurred in mild AD (baseline MMSE 22-26). PE-treated patients also showed less decline on the CDR-sb (71% less decline, P = .002) and ADCS-CGIC (100% less decline, P < .0001).
Why it matters
This trial provides randomized evidence that plasma exchange with albumin and IVIG replacement may slow functional and cognitive deterioration in patients with moderate Alzheimer's disease.
Limits
The cognitive co-primary endpoint (ADAS-Cog) did not reach statistical significance in the full cohort (P = .06), and no benefit was observed in mild AD. The abstract does not provide absolute score changes, confidence intervals, safety/tolerability data, or breakdown by specific albumin/IVIG dose arms.