Burst-Type Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

Study Overview
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Brief Summary
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This is a study to evaluate Deep brain stimulation (DBS) burst-type electrical stimulation programming verses standard DBS programming. Burst-type DBS is defined as a novel stimulation protocol in which intermittent bursts of traditional high-frequency rectangular wave stimulation are delivered. Burst type DBS may improve the efficacy and durability of DBS pulse generator.

Detailed Description
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Five (N = 5) subjects that have bilateral STN-DBS (with Boston Scientific Gevia or Genus technology) implanted for Parkinson's Disease. Subjects should be on stable DBS programming settings and stable medication regimens defined as no DBS programming changes or Parkinson's disease medication changes over 6 months. The DBS implantation should have been performed by either Dr. Nestor D. Tomycz MD or Dr. Donald M. Whiting MD at Allegheny General Hospital and implantation surgery must have occurred a minimum of 6 months prior to the day of enrollment. Screening Visit- All interested patients will undergo a screening visit during which their eligibility into the study will be determined. Screening will including the following: Review and signing of informed consent document. Demographics: Date of birth, Gender, Ethnicity, Handedness Medical history: Surgical/Interventional Procedure History, Parkinson's Disease History (presence of symptoms required for eligibility will be documented), presence and in some cases severity of selected symptoms of either PD or PD medications that can also occur as a side effect of STN DBS dopamine dysregulation syndrome (DDS); Review of current Parkinson's disease medications: Dosage/frequency (Start Date, Stop Date) Review of concomitant medications Visit 1- Baseline (less than or equal to 30 days after Screening Parkinson's disease dopaminergic medications will be withdrawn overnight to establish medication-OFF state and DBS will be turned OFF overnight for establishing DBS-OFF state. Examiner will establish a UPDRS-III baseline with medication-OFF, DBS-OFF state. Unblinded examiner will then turn the DBS ON to the patient's baseline DBS settings continuously ON or to burst DBS mode (baseline DBS settings for the patient with DBS set to 1 sec ON, 4 sec OFF), based on results of randomization. The patient will be blinded to this programming change and will be kept at this initial setting for 30 minutes. Next, a blinded examiner who did not perform the programming change will perform a UPDRS-III evaluation. Next, the DBS will be turned off for 15 minutes to permit for a washout period. Next, the DBS will be turned on by the unblinded examiner to the alternate setting (burst DBS in case that the patient first was turned on with their baseline DBS setting or baseline DBS setting in case that the patient was first turned on with burst DBS setting) and kept on this setting for 30 minutes. After 30 minutes, the blinded examiner will perform another UPDRS-III evaluation. Patients, who are blinded to the stimulation setting, will be asked if they preferred one stimulation mode over the other. If any adverse events occur with burst DBS mode, the unblinded examiner will decrease the amplitude of the DBS by 0.5mA increments until the adverse events abate. If there are not persistent adverse events with 30 minutes of burst DBS mode, the patient will be kept in burst DBS mode at the end of first visit and will be allowed to take their Parkinson's disease medications. Randomization- Subjects will be randomized to determine which DBS setting is initially programmed during visit one. All subjects will be programmed to both settings over the course of the visit, but the order is randomized to ensure appropriate blinding of the UPDRS assessor. Subjects have a 50% chance of being randomized to the burst mode, and a 50% chance of being randomized to the baseline mode. Visit Two (6 months +/- 30 Days) Parkinson's disease dopaminergic medications will be withdrawn overnight to establish medication-OFF state and DBS will be turned OFF overnight for establishing DBS-OFF state. Examiner will establish a UPDRS-III baseline with medication-OFF, DBS-OFF state. Examiner will then turn the DBS ON to the burst DBS state and keep ON for 30 minutes. After 30 minutes the examiner will perform another UPDRS-III evaluation and will ask about any adverse effects. Patients will then be allowed to take their Parkinson's disease medications and will be kept on the burst mode DBS state. Patients will be asked if they prefer the burst mode DBS state to their baseline settings before the study. Visit Three (12 months +/- 30 days) Parkinson's disease dopaminergic medications will be withdrawn overnight to establish medication-OFF state and DBS will be turned OFF overnight for establishing DBS-OFF state. Examiner will establish a UPDRS-III baseline with medication-OFF, DBS-OFF state. Examiner will then turn the DBS ON to the burst DBS state and keep ON for 30 minutes. After 30 minutes the examiner will perform another UPDRS-III evaluation and will ask about any adverse effects. Patients will then be allowed to take their Parkinson's disease medications and will be kept on the burst mode DBS state. Patients will be asked if they prefer the burst mode DBS state to their baseline settings before the study. At the conclusion of the study, patients will be asked if they want to continue to use burst DBS state or if would prefer to be programmed back to their pre-study baseline DBS settings.

Official Title
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Burst-Type Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Pilot Study of Tolerability and Efficacy

Conditions
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Parkinson Disease, Deep Brain Stimulation

Intervention / Treatment
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* Device: Burst-type DBS electrical stimulation programming
* Device: Standard of care DBS programming


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bilateral DBS-STN (subthalamic nucleus) target for idiopathic Parkinson's disease implanted minimum 6 months prior to the day of study enrollment Stable DBS programming settings and Parkinson's disease medications defined as no changes to either within past 6 months Comfortable using DBS controller to turn off device prior to study visits Able to provide informed consent and complete follow-up visits Exclusion Criteria: DBS technology other than Boston scientific Genus/Gevia Unable to complete follow-up visits DBS brain targets other than STN (subthalamic nucleus) Signs of progressive cognitive decline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind cross-over study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of care programming<br>Standard of care DBS electrical stimulation | Device: Standard of care DBS programming<br>* Standard of care DBS stimulation programming<br>* Other names: Boston Scientific Neuromodulation (BSN) Vercise™ System;|
| Experimental: Experimental/Burst-type programming<br>Burst-type DBS electrical stimulation | Device: Burst-type DBS electrical stimulation programming<br>* Burst-type DBS is defined as a novel stimulation protocol in which intermittent bursts of traditional high-frequency rectangular wave stimulation are delivered.<br>* Other names: Boston Scientific Neuromodulation (BSN) Vercise™ System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score | To determine change in the UPDRS-III motor score in the medication OFF state with burst-type DBS programming in the acute setting (after 30 minutes) and then after 6 months and 12 months. Each item is scored on a scale from 0 (normal) to 4 (severe, marked, or unable), with the total possible score for the 14 items, including separate questions regarding symptoms present axially and in appendages, ranging from 0 to 56. A higher score means a worse outcome. | 12 months |