Orally administered epigallocatechin gallate showed no significant benefits in modifying disease progression for people with multiple system atrophy, according to clinical trial results published in The Lancet Neurology.
Investigators designed a randomized, double-blind, placebo-controlled clinical trial (PROMESA; ClinicalTrials.gov Identifier: NCT02008721) to test the safety and efficacy of using epigallocatechin gallate, a component extracted from green tea, for the treatment of multiple system atrophy in people with the prototypic synucleinopathy.
The trial included 12 Parkinson disease care centers in Germany and an exploratory MRI substudy focused on reviewing changes in cerebral volume reduction in affected brain areas between baseline and study completion. Investigators assessed 127 participants between April 23, 2014, and September 3, 2015. Of those recruited, 92 participants were enrolled in the trial (n=47, epigallocatechin gallate; n=45, placebo) and 32 participated in the MRI substudy (n=17, epigallocatechin gallate; n=15, placebo).
Participants were initially titrated on epigallocatechin gallate or a placebo-matched control by the following dosing scheme: 1 capsule in the morning (daily total, 400 mg) for 4 weeks, followed by 1 capsule twice a day (daily total, 800 mg) for the subsequent 4 weeks, and ultimately 1 capsule 3 times per day (daily total, 1200 mg) for the final 4 weeks.
At the conclusion of the 12-week titration period, the investigators assessed for hepatotoxicity (defined as aminotransferase concentrations greater than 3 times the upper limit of normal) to ensure tolerance to the daily 1200-mg dosage for 36 more weeks. In those who continued, treatment was stopped at the 48-week visit and followed by a 4-week “washout” period; final assessment was completed at week 52.
Epigallocatechin gallate was found to be safe but was associated with more frequent increases in aminotransferase concentrations than was placebo. Serious liver toxicity occurred in 4% (n=2) of patients in the treatment group.
The researchers defined the primary end point as a change in participant motor examination score using the Unified Multiple System Atrophy Rating Scale (UMSARS). Baseline to week-52 total scores on UMSARS and motor exam scores revealed no significant difference between epigallocatechin gallate and placebo groups. Change in UMSARS scores from baseline to week 52 was -0.94 points (95% CI, -3.71 to 1.83; P =.51), and the total score difference was -0.02 points (95% CI, -4.79 to 4.76; P =.99).
Weak evidence of therapeutic effect was found for the primary end point in the exploratory MRI substudy (mean difference -5.18 points [95% CI, -9.32 to -1.04; P =.014); however, iron-sensitivity sequences could not be assessed due to technical difficulties at 2 of the 3 imaging sites.
The investigators noted that the findings of the PROMESA trial are limited by the fact that it was not powered to detect smaller changes in UMSARS scores, that the dropout rate was higher than anticipated, and that some care centers recruited small sample sizes, which may have introduced increased variability to findings.
Despite limitations and lack of evidence supporting treatment with epigallocatechin gallate, the investigators reported that “1200 mg epigallocatechin gallate daily is toxic for a substantial proportion of patients with multiple system atrophy.” They go on to note that “studies of higher doses cannot be safely recommended in human beings, and hepatotoxic effects should be screened for in all studies of epigallocatechin gallate.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Levin J, Maaß S, Schuberth M, et al. Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): a randomised, double-blind, placebo-controlled trial [published online July 2, 2019]. Lancet Neurol. doi: 10.1016/S1474-4422(19)30141-3