Randomized trial comparing steered stimulation DBS with ring-shaped DBS for advanced Parkinson’s disease

Rationale: Continuous bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective surgical treatment for patients with advanced Parkinson’s Disease (PD) who have severe limitations in functioning due to medication induced motor response fluctuations. Despite its effectiveness, DBS therapy is oftentimes restricted by side-effects, possibly caused by electrical current overspill into areas of the brain adjacent to the target areas. Recently, new DBS electrodes have been developed that claim to be able to achieve a certain degree of steering of the electrical current (steering electrodes, as opposed to the conventional ring-mode electrodes).

Objective: To evaluate whether steered STN DBS is more effective than ring-mode DBS in reducing PD motor symptoms and to investigate if steered STN DBS has the potential to cause less stimulation-induces side-effects.

Hypothesis: We hypothesize that steering DBS will lead to a greater reduction of PD motor symptoms than ring-mode DBS. We will also separately measure the effect of the two types of DBS in people who have good response to ring-mode and those who don’t.

Study design: The study will be a randomized single-center prospective double-blind, crossover trial comparing two forms of STN deep brain stimulation settings: (1) ring-mode stimulation and (2) steered stimulation. A total of 102 patients will be included.

Study population: Patients with advanced PD who have been bilaterally implanted with Boston® Vercise™ DBS electrodes in the subthalamic nucleus in the AMC.

Intervention: After a period of searching for the optimal steered mode settings, patients will be randomized to receive both steered and ring-mode stimulation in consecutive periods of two months in random order. The patient, the assessor and the investigator performing the statistical analyses will be blind to the order in which the two settings are administered.

Main study parameters/endpoints: We will evaluate the difference of motor symptoms in patients with steered and ring-mode DBS in standardized OFF-drug phase measured with the Movement Disorders Society Unified Parkinson Disease Rating Scale motor evaluation (MDS-UPDRS-ME). Secondary outcome consists of symptom scales, used stimulation settings, medication use, stimulation-induced side-effects, activities of daily living scales and a quality of life questionnaire. At the end of the trial, patients will be asked to choose between the two used programs to evaluate which one was perceived as the best. A sub-analysis will be performed to evaluate whether good DBS responders and suboptimal DBS responders score differently on primary and secondary endpoints.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study will contribute to the optimization of DBS treatment with devices that allow for current steering. The hardware and software that will be used in the course of the study are CE approved, and DBS has been a registered therapy for PD for years. In this study, new programming options will be explored, which will extend the device programming time. There is a small chance/risk that the steering DBS form will have less benefit to the patient’s motor score when compared to ring-mode DBS or that patients will be subjected to a longer programming time with no additional clinical benefit. Participation in this study constitutes a negligible risk according to the NFU-criteria for human research.

We hypothesize that steering DBS will lead to a greater reduction of PD motor symptoms than ring-mode DBS. We will also separately measure the effect of the two types of DBS in people who have good response to ring-mode and those who don’t.

• (informed consent)

• Baseline

• Visites tijdens instelperiode van “steering-settings”

• Randomisatievisite

• Cross-over visite

• Release visite

After a period of searching for the optimal steered mode settings, patients will be randomized to receive both steered and ring-mode stimulation in consecutive periods of two months in random order. The patient, the assessor and the investigator performing the statistical analyses will be blind to the order in which the two settings are administered.