Plasma exchange for Alzheimer's disease Management by Albumin Replacement (AMBAR) trial: Study design and progress
Plasma exchange for Alzheimer's disease Management by Albumin Replacement (AMBAR) trial: Study design and progress
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DOI：
10.1016/j.trci.2019.01.001
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Paez, Antonio
中科院分区：
文献类型：
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作者：
Boada, Merce;Lopez, Oscar;Paez, Antonio
前言：初步研究表明，血浆置换(PE)加治疗性白蛋白替代治疗阿尔茨海默病(AD)患者可诱导血浆和脑脊液淀粉样β蛋白的动员，与记忆和语言功能的改善以及脑血流灌注的稳定有关，并在治疗中断后持续。方法：通过白蛋白替代治疗阿尔茨海默病(AMBAR)是一项多中心、随机、双盲和安慰剂对照的平行分组IIb/III期试验，纳入轻至中度AD患者。这项研究评估了不同替代量的治疗性白蛋白(5%和20%Albutein(R)，Grifols)，使用或不使用静脉免疫球蛋白(FleboGamma(R)5%DIF，Grifols)。患者被随机分为三个积极治疗组或一个对照组(假PE组)(1：1：1：1)。干预方案包括第一个为期6周的强化治疗阶段，然后是第二个为期12个月的维持治疗阶段。ADAS-Cog和ADCS-ADL评分中从基线到疗程结束的变化是主要的疗效变量。次要疗效变量包括认知、功能、行为和总体进展测试中基线分数的变化；血浆和脑脊液中淀粉样β蛋白和tau蛋白水平的变化；以及对大脑感兴趣区域的结构和功能变化的评估。结果：该研究从41个中心(西班牙19个，美国22个)招募了496名患者；其中347名患者随机接受了近5000例PE，其中约25%是假PE。这项研究旨在证明临床疗效，其定义是患者认知和脑功能的缓慢下降。样本量具有足够的能力来检测任何有效治疗组与对照组之间的差异，以及三个有效治疗组组合与对照组之间的差异。(C)2019年提交人。由爱思唯尔公司代表阿尔茨海默氏症协会出版。
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 beta 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 (R), Grifols), with or without intravenous immunoglobulin (Flebogamma (R) 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 beta 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. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.