GM1 Ganglioside Therapy in Acute Ischemic Stroke

Abstract

A double-blind, randomized, placebo-controlled clinical trial, involving two Italian centers, was carried out to evaluate the efficacy and safety of the monosialoganglioside GM1 in acute ischemic stroke. A total of 112 consecutive patients were recruited. The treatment (GM1 or placebo) was intravenously administered for 3 weeks and the follow-up lasted for 6 months. Semiquantitative clinical evaluations were performed on admission at the end of treatment (day 21) and at the end of follow-up (day 180), by using the Frithz-Werner Scale for the neurological recovery and the Barthel Index for the activities of daily living. On day 21, the statistical analysis showed a significant neurological improvement (p < 0.01) in the Frithz-Werner Scale in favor of the GM1 group. On day 180, the difference between the two groups was not significant for the Frithz-Werner Scale, while it reached significance for the activities of daily living (Barthel Index) in favor of the GM1-treated group (p < 0.05).

GM1 Ganglioside for Acute Ischemic Stroke: Trial Design Issues

“…However, it is likely that injection‐site reactions occur more often when the intramuscular route is used. An allergic reaction was reported in one patient by Angeleri et al , 9 and one patient who received GM 1 in the EST trial 13 developed an acute ascending polyradiculopathy (Guillain‐Barré syndrome). Other isolated reports of Guillain‐Barré syndrome (GBS) have raised concerns in some European countries sufficient to result in suspension of the drug's distribution, but this concern is mitigated by the fact that after analysis, many of the anecdotal reports of GBS referred to patients who had received GM 1 after symptoms had started or there were conditions prior to use of GM 1 such as diarrhea, perhaps from Campylobacter jejuni that could have been the cause of the GBS.…”

“…In order to obtain convincing evidence of efficacy, clinical trials of GM 1 in acute stroke were initiated more than a decade ago. In this paper, I have focused first on the randomized, double‐blind, placebo‐controlled trials as in the five early trials listed in Table 1: three (references 7–9) concluded that GM 1 was efficacious, whereas two (references 10 and 11) concluded that there were no significant differences between patients who were given GM 1 and those given placebo. However, one of the latter (reference 10) did show that patients who received GM 1 did slightly better than the placebo‐treated group, although the difference was not statistically significant.…”

“…In two trials, treatment continued for 6 weeks. Inspection of the curve of improvement over this period in at least three trials (references 9, 12, 14) (Figs. 1, 2, and 5) has shown that the group that received GM 1 was improving at a faster rate than the placebo‐treated group as long as treatment continued.…”

“… Efficacy: Comparison of GM 1 ‐ and placebo‐treated patients on Frithz‐Werner Scale (FW) in Angelieri et al 's 9 study. …”