CUSTOM-DBS: Current Steering to Optimize Deep Brain Stimulation

Study Overview
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Brief Summary
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The objective of the study is to compare different deep brain stimulation (DBS) settings using the commercially approved Boston Scientific Neuromodulation Vercise system.

Detailed Description
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The study is a prospective, multi-center, double-blind, randomized controlled trial. This study will compare various program settings for the bilateral stimulation of the STN using the BSC implantable Vercise™ DBS System for the treatment of levodopa-responsive, moderate to severe idiopathic PD.

Official Title
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Current Steering to Optimize Deep Brain Stimulation

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: Vercise DBS settings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Implanted bilaterally in STN with a Vercise DBS system for Parkinson's disease for at least three months with programming optimized according to standard of care. UPDRS subset III score of ≥30 in the in the pre-operative meds off state. DBS must improve PD symptoms by ≥30% in the meds off state, as measured by UPDRS subset III score. Medical and mental fitness to comply with programming visit and study related procedures. Able to understand the study requirements and the treatment procedures and provides written informed consent before any study-specific tests or procedures are performed. Off symptom rigidity score of ≥2 in the evaluated arm as determined by the UPDRS-III. Exclusion Criteria: Have any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints, including any terminal illness with survival <12 months. Resting and/or action tremor score of ≥3 on the evaluated side as determined by the UPDRS-III in pre-operative meds off condition.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short PW<br>Patients with a Vercise DBS system programmed to 30 microseconds pulse width | Device: Vercise DBS settings<br>* Deep brain stimulation set at short pulse width and monopolar stimulation using current steering<br>|
| Experimental: Conventional PW<br>Patients with a Vercise DBS system programmed to 60 microseconds pulse width | Device: Vercise DBS settings<br>* Deep brain stimulation set at short pulse width and monopolar stimulation using current steering<br>|
| Experimental: Ventral current steering<br>Patients with a Vercise DBS system programmed to steer current ventrally | Device: Vercise DBS settings<br>* Deep brain stimulation set at short pulse width and monopolar stimulation using current steering<br>|
| Experimental: Dorsal current steering<br>Patients with a Vercise DBS system programmed to steer current dorsally. | Device: Vercise DBS settings<br>* Deep brain stimulation set at short pulse width and monopolar stimulation using current steering<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic Window | The therapeutic window refers to the range of stimulus amplitudes that provide a therapeutic effect without side effects. In other words, it is the amplitude difference between the first stimulation-induced side effect threshold (e.g., eye deviation, muscle contraction, and speech) and full rigidity control threshold at 60 µs and 30 µs pulse width DBS settings. | Day 1 programming visit | 
| Unified Parkinson's Disease Rating Scale III | The Unified Parkinson's Disease Rating Scale (UPDRS) has four sections (I-IV) that ask patients to rate aspects of their mental state including mood (I), aspects of daily activities (II), aspects of motor function (III), and complications of treatment (IV). Here, we ask subjects to rate their motor function (UPDRS III) following interventions with 30 µs and 60 µs pulse width DBS settings. The UPDRS III scale has 14 categories including speech, facial expression, tremor at rest, action tremor, rigidity, finger tapping ability, ability to open and close hands, ability to rapidly alternate hand movements, leg agility, ability to rise from a chair, posture, gait, response to postural displacement (e.g., push), and bradykinesia. Patients rate each of these categories from 0 to 4, with 0 being normal function and 4 being the worst. Categories assessing appendages are rated for both left and right sides, allowing a maximum score (worst outcome) of 108. | Day 1 programming visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side Effect Thresholds - Single Contact vs. Steering | This endpoint determined how much current (mA) could be applied before side effects appeared when using 60 microsecond pulse widths. Values were obtained for when current was delivered through a single contact or divided between two contacts (steering). | Day 1 programming visit | 
| Resting Tremor Severity - Single Contact vs. Steering | Resting tremor was measured by a motion sensor system (Kinesia System) while either using a single contact or steering current between two contacts. Stimulation was at amplitudes defined as the therapeutic threshold for rigidity. The Kinesia System was worn by patients to measure motion parameters including linear acceleration and angular velocity during different tasks, then provided an output score on a scale of 0 (no symptoms) to 4 (severe symptoms). | Day 1 programming visit | 
| Finger Tapping Amplitude - Single Contact vs. Steering | Severity of finger-tapping bradykinesia was measured by a motion sensor system (Kinesia System) when either using a single contact or steering current between two contacts. Stimulation was at amplitudes defined as the therapeutic threshold for rigidity. The Kinesia System was worn by patients to measure motion parameters including linear acceleration and angular velocity during different tasks, then provided an output score on a scale of 0 (no symptoms) to 4 (severe symptoms). | Day 1 programming visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stimulation, implantable pulse generator, deep brain stimulation