Randomized Trial on DBS Programming Based on Biomarkers vs. Standard Monopolar Review

Deep brain stimulation (DBS) is an established therapy for patients with Parkinson's disease (PD) with motor fluctuations inadequately controlled by medication. However, DBS programming is currently based on monopolar review, a time-consuming process that relies heavily on clinician experience and subjective patient feedback. This approach does not systematically incorporate objective anatomical or neurophysiological information regarding the optimal stimulation contact and may require several months to achieve satisfactory clinical benefit.

Recent advances in DBS technology allow the integration of objective markers into the programming process. These include postoperative anatomical reconstruction of electrode location using neuroimaging and the recording of local field potentials (LFPs), particularly beta-band activity, from implanted DBS systems. In parallel, wearable inertial sensors enable continuous, objective quantification of motor states such as OFF time, dyskinesias, motor fluctuations, and gait disturbances in daily life.

This study is a pilot, randomized, controlled, parallel-group clinical trial with single-blind assessment, designed to evaluate whether DBS programming guided by objective markers (electrode localization on neuroimaging combined with beta LFP sensing) improves clinical outcomes compared with conventional programming based on monopolar clinical review. The study will be conducted in patients with Parkinson's disease undergoing DBS surgery at the Movement Disorders Unit of the Hospital de la Santa Creu i Sant Pau.

A total of 20 participants with idiopathic Parkinson's disease will be enrolled and randomized in a 1:1 ratio to one of two programming strategies: (1) conventional DBS programming based on clinical monopolar review, or (2) DBS programming guided by anatomical electrode reconstruction using Brainlab Elements™ and neurophysiological beta biomarkers obtained via BrainSense™. All participants will be implanted with a clinically approved DBS system (Percept™ PC or RC with SenSight™ directional leads, Medtronic) and will wear PDMonitor® inertial sensors for objective motor assessment. The only difference between groups is the DBS programming strategy.

All participants will undergo a 7-day PDMonitor® recording and a full clinical evaluation during the preoperative visit. DBS surgery will be followed by an approximately one-month postoperative period without stimulation. Initial DBS programming will begin around week 5 after surgery. A mid-programming clinical evaluation and PDMonitor® recording will be performed at approximately week 9. At 3 months after initiation of programming, participants will complete another 7-day PDMonitor® recording and a full clinical assessment, which will serve as the primary endpoint evaluation. Adaptive DBS (aDBS) will then be activated in both groups. A final follow-up visit at 6 months will include clinical assessments and sensor-based measurements; these post-aDBS data will be analyzed descriptively and exploratorily only.