Plasma exchange for Alzheimer's disease Management by Albumin Replacement (AMBAR) trial: Study design and progress.

INTRODUCTION: Preliminary studies have shown that treatment with plasma exchange (PE) plus therapeutic albumin replacement in patients with Alzheimer's disease (AD) induced mobilization of plasma and cerebrospinal fluid amyloid ß protein, associated with an improvement in memory and language functions, as well as the stabilization of brain perfusion, which persisted after treatment discontinuation. METHODS: Alzheimer's Management By Albumin Replacement (AMBAR) is a multicenter, randomized, blinded and placebo-controlled, parallel-group, phase IIb/III trial enrolling patients with mild to moderate AD. The study evaluates PE with different replacement volumes of therapeutic albumin (5% and 20% Albutein®, Grifols), with or without intravenous immunoglobulin (Flebogamma® 5% DIF, Grifols). Patients are randomized to one of three active treatment groups or one control (sham PE) group (1:1:1:1). The intervention regime includes a first 6-week stage of intensive treatment, followed by a second 12-month stage of maintenance treatment. The change from the baseline to the end of treatment periods in the ADAS-Cog and ADCS-ADL scores are the coprimary efficacy variables. Secondary efficacy variables include change from the baseline in scores on cognitive, functional, behavioral, and overall progression tests; changes in plasma and cerebrospinal fluid levels of amyloid ß and tau protein; and assessment of structural and functional changes in brain areas of interest. Safety and tolerability are assessed. RESULTS: The study has enrolled 496 patients from 41 centers (19 in Spain and 22 in the USA); 347 of these patients were randomized and underwent close to 5000 PEs, of which approximately 25% were sham PEs. DISCUSSION: We present an innovative approach for treating AD. The study has been designed to demonstrate clinical efficacy, defined as slow decline of the patient's cognition and brain function. The sample size has adequate power to detect differences between any of the active treatment groups and the control group, as well as between the three active treatment groups combined and the control group.