Objective: To analyze symptomatic control of rest tremor five years after randomization in the deep brain stimulation (DBS) in early-stage Parkinson’s disease (PD) pilot clinical trial.

Background: This trial provided class II evidence that DBS implanted in very early PD slows the progression of rest tremor [1]. A week-long therapeutic washout at baseline and every six months for two years after randomization was used to evaluate changes in underlying motor symptoms (off-therapy). Participants then completed annual on-therapy visits through five years to collect additional safety data.

Method: The pilot was a prospective, single-blind clinical trial that randomized early-stage PD subjects (Hoehn & Yahr II off medications) to receive DBS plus optimal drug therapy (ODT) versus ODT alone (IDEG050016, NCT0282152, IRB040797).  Among the 15 subjects randomized to ODT, one dropped out after baseline and four elected to receive subthalamic nucleus (STN) DBS during the extension follow-up period. For this analysis, subjects with a medication duration of 6 months–4 years at enrollment were evaluated in the treatment group to which they were randomized (early ODT=14; early DBS+ODT=14). A proportional odds logistic regression model was used with rest tremor score (UPDRS-III item 20 on-therapy) as the outcome and baseline score, time, and treatment assignment as independent variables. A linear mixed effects model was used to compare rest tremor scores with fixed effects of baseline value, time, and treatment assignment, random effects of subjects, and an autoregressive covariance structure to account for within-subject repeated measures.

Results: The odds of having worse rest tremor was 5-fold lower for the early DBS+ODT group than the early ODT group (P<0.001, OR=0.20, 95% CI: 0.09 to 0.45). Additionally, at five years, the early DBS+ODT group had a significantly lower rest tremor score than the early ODT group (P=0.005, estimate = -2.03, 95% CI: -3.38 to -0.67).

Conclusion: These results suggest that, in addition to slowing the progression of rest tremor, early DBS may also provide long-term rest tremor benefit compared to standard medical care. The FDA has approved the conduct of a prospective, multicenter, double-blind, phase III, pivotal trial of DBS in early-stage PD.

References: [1] Hacker et al., Neurology 2018 91(5):e463-e471.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-in-early-stage-parkinsons-disease-provides-long-term-rest-tremor-benefit-through-five-years/