Clinical trial NCT05753449: Burst-Type Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease
Official title: Burst-Type Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Pilot Study of Tolerability and Efficacy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Parkinson Disease
Deep Brain Stimulation
Lead sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2023-03-03
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, double-blind cross-over study
Primary purpose: TREATMENT

Brief summary: 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: Five (N = 5) subjects that have bilateral subthalamic nucleus deep brain stimulation (STN-DBS), with Boston Scientific Gevia or Genus technology, implanted for Parkinson's Disease (PD). 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 the past 2 weeks. 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 0.5 milliamp (mA) 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.

Eligibility criteria: 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 2 weeks
* 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

Primary outcomes:
measure: Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Baseline (Visit 1)
timeFrame: Baseline
measure: Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Six Months (Visit 2)
timeFrame: 6 months
measure: Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Twelve Months (Visit 3)
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: AHN Allegheny General Hospital
state: Pennsylvania
Study officials:
affiliation: Allegheny Health Network AGH Department of Neuroscience
name: Nestor Tomycz
role: PRINCIPAL_INVESTIGATOR
References: