Objective: To report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial.

Methods: The pilot was a prospective, single-blind clinical trial that randomized patients with early-stage PD (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) vs ODT alone (IDEG050016, NCT0282152, IRB040797). Participants who completed the 2-year trial participated in this observational follow-up study, which included annual outpatient visits through 5 years. This analysis includes 28 patients who were taking PD medications for 6 months to 4 years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models.ResultsEarly STN DBS + ODT participants required lower levodopa equivalent daily doses (p = 0.04, β = −240 mg, 95% confidence interval [CI] −471 to −8) and had 0.06 times the odds of requiring polypharmacy at 5 years compared to early ODT participants (p = 0.01, odds ratio [OR] 0.06, 95% CI 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS + ODT participants were 0.21 times those of early ODT participants (p < 0.001, OR 0.21, 95% CI 0.09 to 0.45). The safety profile was similar between groups.

Conclusions: These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the Food and Drug Administration has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016).

Classification of evidence: This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.

The STN DBS in early PD pilot was a prospective, randomized, controlled, single-blind clinical trial (ClinicalTrials.gov NCT00282152) that was approved by the FDA (IDEG050016) and Vanderbilt IRB (IRB040797). All 29 subjects who completed the two-year pilot trial provided written informed consent to participate in an observational follow-up study that included annual outpatient visits at three, four, and five years after baseline (IRB040797).

All adverse events (AEs) collected at years three, four, and five were coded using the preferred term in the Medical Dictionary for Regulatory Activities (MedDRA)21 and classified as mild, moderate, severe and/or serious.