没食子酸表没食子儿茶素酯在复发缓解型多发性硬化症中的应用：一项随机、安慰剂对照试验。
Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis: A Randomized, Placebo-Controlled Trial.
机构信息
From the NeuroCure Clinical Research Center (J.B.-S., F.P., J.D., A.B., V.S.), Charité-Universitätsmedizin Berlin; Medical Image Analysis Center (J.W.), University Basel; Institut for Medical Immunology (C.I.-D., E.H.), Charité-Universitätsmedizin Berlin; Department of Neurology and Neuroimaging Center (B.K.), Johannes Gutenberg University, Mainz; Charité-Universitätsmedizin Berlin (C.P.); NeuroCure Clinical Research Center (H.R., R.R.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (O.A.), Medical Faculty, Heinrich Heine University Düsseldorf; Institut für Neuroimmunologie und Multiple Sklerose (C.H.), Universitätsklinikum Hamburg-Eppendorf, Hamburg; Klinik für Neurologie (J.F.), Asklepios Klinik Lübben/Teupitz; Department of Neurology (F.H.), Krankenhaus Martha-Maria Halle-Dölau, Halle/Saale; Medizinische Klinik für Kardiologie und Angiologie (M.L.), Campus Mitte, Charité-Universitätsmedizin Berlin; Institute of Nutritional and Food Sciences (B.Z.), University of Bonn; Department of Neurology and Neuroimaging Center (NIC) (S.G., F.Z.), Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University, Mainz; and Charité-Universitätsmedizin Berlin and SOSTANA GmbH (K.-D.W.), Berlin.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2021 Mar 24;8(3). doi: 10.1212/NXI.0000000000000981. Print 2021 May.
OBJECTIVE
To assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS
We enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospective, double-blind, phase II, randomized controlled trial. Participants received up to 800 mg oral EGCG daily over a period of 18 months. The primary outcome was the proportion of patients without new hyperintense lesions on T2-weighted (T2w) brain MRI within 18 months. Secondary end points included additional MRI and clinical parameters. Immunologic effects of EGCG were investigated in exploratory experiments.
RESULTS
A total of 122 patients on GA were randomly assigned to EGCG treatment (n = 62) or placebo (n = 60). We could not demonstrate a difference between groups after 18 months for the primary outcome or other radiologic (T2w lesion volume, T1w hypointense lesion number or volume, number of cumulative contrast-enhancing lesions, percent brain volume change), or clinical (EDSS, MS functional composite, and annualized relapse rate) parameter. EGCG treatment did not affect immune response to GA. Pharmacologic analysis revealed wide ranging EGCG plasma levels. The treatment was well tolerated with a similar incidence of mostly mild adverse events similar in both groups.
CONCLUSION
In RRMS, oral EGCG add-on to GA was not superior to placebo in influencing MRI and clinical disease activity over 18 months. The treatment was safe at a daily dosage up to 800 mg EGCG. It did not influence immune parameters, despite indication of EGCG being bioavailable in patients.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that for patients with RRMS, EGCG added to GA did not significantly affect the development of new hyperintense lesions on T2-weighted brain MRI.
TRIAL REGISTRATION INFORMATION
Clinical trial registration number: NCT00525668.
目的
评估表没食子儿茶素没食子酸酯（EGCG）加用格拉替雷（GA）治疗复发缓解型多发性硬化（RRMS）患者的安全性和有效性。
方法
我们纳入了年龄在 18-60 岁之间、接受稳定 GA 治疗的 RRMS 患者（扩展残疾状态量表[EDSS]评分 0-6.5），并在一项多中心、前瞻性、双盲、II 期、随机对照试验中进行了研究。参与者接受了为期 18 个月的每日 800 毫克口服 EGCG 治疗。主要终点是 18 个月内无新 T2 加权（T2w）脑 MRI 高信号病变的患者比例。次要终点包括其他 MRI 和临床参数。在探索性实验中研究了 EGCG 的免疫效应。
结果
共有 122 名 GA 患者被随机分配到 EGCG 治疗组（n=62）或安慰剂组（n=60）。在 18 个月后，我们未能证明两组在主要终点或其他影像学（T2w 病变体积、T1w 低信号病变数量或体积、累积增强病变数量、脑容量变化百分比）或临床（EDSS、MS 功能综合评分和年复发率）参数方面存在差异。EGCG 治疗并未影响对 GA 的免疫反应。药物分析显示 EGCG 血浆水平广泛。该治疗具有良好的耐受性，两组不良反应发生率相似，主要为轻度不良反应。
结论
在 RRMS 中，GA 加用口服 EGCG 在 18 个月内对 MRI 和临床疾病活动的影响并不优于安慰剂。在每日 800 毫克 EGCG 的剂量下，治疗是安全的。尽管提示 EGCG 在患者中具有生物利用度，但它并未影响免疫参数。
证据分类
这项研究提供了 II 级证据，表明对于 RRMS 患者，GA 加用 EGCG 不会显著影响 T2w 脑 MRI 上新的高信号病变的发展。
临床试验注册号
NCT00525668。
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