Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis

Abstract

ObjectiveTo assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe 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.ResultsA 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.ConclusionIn 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 EvidenceThis 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 InformationClinical trial registration number: NCT00525668.

Retinal Thickness Analysis in Progressive Multiple Sclerosis Patients Treated With Epigallocatechin Gallate: Optical Coherence Tomography Results From the SUPREMES Study

“…Other clinical trials also failed to show a treatment effect of EGCG: The SUNIMS trial ( 63 ) reported no treatment effect of EGCG on clinical or MRI measures in RRMS patients. Moreover, a recently published study demonstrated no impact of EGCG after 48 weeks of treatment on disease progression in multiple system atrophy ( 64 ).…”

Therapeutic Effects of Catechins in Less Common Neurological and Neurodegenerative Disorders

“…Their efficacy endpoint was the development of new hyperintense lesions on T2-weighted brain MRIs. The 18-month treatment with 800 mg/day oral EGCG added to GA showed no superiority in MRI findings and clinical activity, compared to placebo [ 54 ]. A double-blind clinical trial analyzed the mechanisms of antioxidant therapy on MS patients.…”

“…They found that the administration of 800 mg of EGCG on a daily basis for six months increased N-acetyl aspartate levels in the brain, revealing a neuroprotective effect; however, the study had to be stopped because five out of seven patients on the Polyphenon E group had abnormal liver function tests and the researchers concluded that Polyphenon E may increase the risk of hepatotoxicity [ 58 ]. In other reviewed articles, safety of EGCG treatment was assessed, concluding that it was a safe medication with similar adverse events in the placebo and treatment groups [ 54 , 55 ]. Polyphenon E contains other polyphenols besides EGCG and may have small amounts of caffeine, metabolized in the liver, which may explain these safety differences.…”

Prediction of combination therapies based on topological modeling of the immune signaling network in multiple sclerosis

“…We recruited 255 subjects including 195 patients with MS and 60 healthy controls in a multi-centric study in four MS centers (Hospital Clinic Barcelona -IDIBAPS (n=69), Karolinska Institute (n=64), University of Zurich (n=40), and Charité University (n=82)). Healthy donors, untreated patients and patients treated with IFNB, GA, NTZ, and FTY were described before in an accompanying study [26], whereas the participants in a trial testing epigallocatechin-gallate (EGCG) at Charité University were described in [27]. Characteristics of the clinical cohorts: mean age: 43.1+11.3 years; disease duration: 8.7+ 7.7 years; median Expanded Disability Status Scale (EDSS): 2.0 (0-6.0); disease subtype: 24 clinically isolated syndrome (CIS), 129 relapsing-remitting MS (RRMS), 6 secondary-progressive MS (SPMS), and 36 primaryprogressive MS (PPMS); untreated: 93 and 60 healthy controls (Table 2).…”

“…The data from clinical studies has been published by Kotelnikova et al in [26], while the data from the EGCG clinical trial has been published by Bellmann-Strobl et al in [27]. All data generated in this study are available on Github (http://github.com/saezlab/combiMS) [73], including all data transformations from xMAP raw measurements to modelling-transformed as shown in Fig.…”