A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients

Abstract

The present single center, double-blind, delayed start study was conducted to examine possible symptomatic and disease-modifying effects of GM1 ganglioside in Parkinson's disease (PD). Seventy-seven subjects with PD were randomly assigned to receive GM1 for 120 weeks (early-start group) or placebo for 24 weeks followed by GM1 for 96 weeks (delayed-start group). Washout evaluations occurred at 1 and 2 years after the end of treatment. Seventeen additional subjects who received standard-of-care were followed for comparative information about disease progression. Primary outcome was change from baseline Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. At week 24, the early-start group had significant improvement in UPDRS motor scores vs. a significant worsening of scores in the delayed-start group. The early-start group also showed a sustained benefit vs. the delayed-start group at week 72 and at week 120. Both groups had significant symptom worsening during washout. This study provides evidence that GM1 use for 24 weeks was superior to placebo for improving motor symptoms and that extended GM1 use (up to 120 weeks) resulted in a lower than expected rate of symptom progression. The data from this small study suggest that GM1 may have symptomatic and potentially disease modifying effects on PD.

Figure 1

Subject disposition.

Figure 2

Changes in Unified Parkinson’s Disease Rating Scale (UPDRS) Motor Subsection Scores. A. The mean (±SEM) change from baseline (observed scores) in Early-start and Delayed-start study subjects and in the standard-of-care Comparison group, assessed in the practically defined “off’ condition. The dashed vertical line at week 24 indicates the end of study Phase I. The dashed vertical line at week 120 indicates the end of study Phase II. The horizontal dashed line indicates baseline level. An increase of score indicates symptom worsening; a decrease in score indicates symptom improvement. * = p < 0.0001 Early-start vs. Delayed-start; ^ = p < 0.05 Early-start vs. Delayed-start. B. The mean (±SEM) change from baseline in Early-start and Delayed-start study subjects and in the standard-of-care Comparison group, assessed in the best “on” condition. The dashed vertical line at week 24 indicates the end of study Phase I. The dashed vertical line at week 120 indicates the end of study Phase II. The horizontal dashed line indicates baseline level. * = p < 0.01 Early-start vs. Delayed-start.

Figure 3

Percent of study subjects showing clinically important differences in UPDRS motor subsection scores. Graphs indicate the percent of subjects judged to have minimal (≥2.5 points), moderate (≥5.2 points), large (≥10.8 points) or no (<2.5 points) clinically important change in UPDRS motor scores compared to baseline. Solid bars indicate early-start subjects; shaded bars indicate delayed-start subjects. Week 24 = end of the placebo-controlled phase of the study; Week 36 = 12 weeks after delayed-start group began GM1 use; Week 72 = approximately 1 year after start of Phase II of the study; Week 120 = approximately 2 years after start of Phase II of the study.