Imaging-based versus threshold assessment-based deep brain stimulation programming in Parkinson’s disease: study protocol for a randomized controlled trial {1a}

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) effectively treats motor fluctuations in Parkinson's disease. The clinical outcome depends on optimal programming, which involves selecting active contacts and adjusting stimulation parameters to maximize clinical benefit while minimizing adverse effects. The conventional clinically guided approach, the monopolar review (MPR), is complex and time-consuming due to numerous parameter combinations, interindividual anatomical variability, and differences in DBS lead placement. Recent advances in neuroimaging offer the potential to guide contact selection based on patient-specific anatomy. METHODS: A single-centre, prospective, randomized, open-label trial with blinded endpoint assessment (PROBE design) is being conducted in patients with Parkinson's disease undergoing STN-DBS to determine whether imaging-based contact selection is non-inferior to the current standard MPR for contact selection in treating motor symptoms. A total of 132 patients are randomized to either imaging-based programming (Imaging group) or threshold-assessment-based programming (i.e., MPR, Threshold group). In the Imaging group, contacts are selected using patient-specific 3D anatomical models derived from preoperative 7 T MRI and postoperative CT, visualizing the STN and simulating volumes of tissue activated (VTA) aligned with the motor subdivision. The primary outcome is the mean change from baseline to 6 months in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score during the off-drug phase. Secondary outcomes include motor symptoms in the on-medication phase, duration of off-medication time, dyskinesia severity and duration, non-motor symptoms, motor aspects of daily living, physical disability, disease-specific quality of life, (severe) adverse effects, treatment satisfaction and burden, crossover to the alternate programming arm, use of care, programming duration, final DBS settings, and concordance between 6-months stimulation contacts and initial selections. Follow-up is 6 months after initial programming. DISCUSSION: The trial evaluates whether imaging-based DBS programming can achieve motor improvements comparable to clinical threshold-assessment-based programming, while potentially offering greater efficiency, speed, and stability of stimulation settings. Although the study is designed as a non-inferiority trial, we hypothesize that imaging-based contact selection may ultimately provide a superior approach by enabling faster optimization with fewer parameter adjustments. TRIAL REGISTRATION: The DBS-ITAP trial was registered at clinicaltrials.gov (NCT06223399) on January 23, 2024, https://clinicaltrials.gov/study/NCT06223399.