Deep Brain Stimulation, Parkinson Disease
Conditions
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Visit 1- Baseline (less than or equal to 30 days after Screening * Parkinson's disease dopaminergic medications will be withdrawn overnight to establish medication-OFF state and DBS will be turned OFF overnight for establishing DBS-OFF state.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.
Interventions
DEVICEBaseline (or standard of care) DBS programming
Baseline (or standard of care) DBS programming.
DEVICEBurst-type DBS electrical stimulation programming
Burst-type DBS is defined as a novel stimulation protocol in which intermittent bursts of traditional high-frequency rectangular wave stimulation are delivered.
Sponsors
Boston Scientific Corporation
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Subjects will be programmed to both settings over the course of the visits, but the order is randomized to ensure appropriate blinding of the UPDRS assessor. Unblinded examiner will then turn the DBS ON to the patient's baseline DBS settings continuously ON or to burst DBS mode. A blinded examiner who did not perform the programming change will perform a UPDRS-III evaluation
Intervention model description
Randomized, double-blind cross-over study
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Baseline (Visit 1) | Baseline | This outcome is the Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score in the Medication Off state, after the first treatment (administered for 30 minutes) and after the second treatment (administered for 30 minutes). For example, the first treatment for patients in the arm Baseline Programming First, Then Experimental Burst-type Programming was baseline (or standard of care) DBS programming, and the second treatment was experimental Burst-style programming. 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 108. A higher score indicates a worse outcome. |
| Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Six Months (Visit 2) | 6 months | This outcomes is the Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score in the Medication Off state and after burst-type DBS programming in the acute setting (after 30 minutes) at six 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 108. A higher score means a worse outcome. Note that the study arm titles refer to whether or not the patients were randomized to baseline programming or Burst-type programming at Visit 1. During this visit (Visit 2), all study subjects were to be evaluated in the medication-off state and then evaluated following 30 minutes of treatment with Burst-type programming. Treatment with baseline programming was not administered during this visit (Visit 2). |
| Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Twelve Months (Visit 3) | 12 months | This outcomes is the Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score in the Medication Off state and after burst-type DBS programming in the acute setting (after 30 minutes) at 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 108. A higher score means a worse outcome. Note that the study arm titles refer to whether or not the patients were randomized to baseline programming or Burst-type programming at Visit 1. During this visit (Visit 2), all study subjects were to be evaluated in the medication-off state and then evaluated following 30 minutes of treatment with Burst-type programming. Treatment with baseline programming was not administered during this visit (Visit 2). |
Countries
United States
Participant flow
Recruitment details
2 subjects were recruited in the medical clinic between August 24, 2022, and February 21, 2024. Recruitment ended as we encountered significant challenges in recruiting participants for the study finding reluctance of patients who have achieved successful outcomes with their deep brain stimulation (DBS) devices to participate. They are understandably hesitant to risk potential symptom worsening by altering their device settings, even for the purpose of research.
Participants by arm
| Arm | Count |
|---|---|
| Baseline Programming First, Then Experimental Burst-type Programming In this arm, patients were randomized to initially receive treatment with baseline DBS programming (standard of care) at Visit 1. After a 30 minute treatment period, patients were to undergo UPDRS III evaluation, a 15 minute washout period with the DBS turned off and then experimental Burst-type programming for 30 minutes. Finally, patients were to undergo UPDRS III evaluation after the second round of programming. | 0 |
| Experimental Burst-type Programming First, Then Baseline Programming In this arm, patients were randomized to initially receive treatment with experimental Burst-type DBS programming at Visit 1. After a 30 minute treatment period, patients were to undergo UPDRS III evaluation, a 15 minute washout period with the DBS turned off and then baseline programming (standard of care) for 30 minutes. Finally, patients were to undergo UPDRS III evaluation after the second round of programming. Burst-type DBS is defined as a novel stimulation protocol in which intermittent bursts of traditional high-frequency rectangular wave stimulation are delivered. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Experimental Burst-type Programming First, Then Baseline Programming | Total | Baseline Programming First, Then Experimental Burst-type Programming |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Continuous | 70 years | 70 years | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | — |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 2 |
Outcome results
Primary
Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Baseline (Visit 1)
This outcome is the Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score in the Medication Off state, after the first treatment (administered for 30 minutes) and after the second treatment (administered for 30 minutes). For example, the first treatment for patients in the arm Baseline Programming First, Then Experimental Burst-type Programming was baseline (or standard of care) DBS programming, and the second treatment was experimental Burst-style programming. 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 108. A higher score indicates a worse outcome.
Time frame: Baseline
Population: No subjects were randomized to the arm that received baseline (standard of care) programming first, followed by experimental Burst-style programming (at Visit 1).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental Burst-type Programming First, Then Baseline Programming | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Baseline (Visit 1) | Medication-Off and DBS-Off State | 55.5 score on a scale |
| Experimental Burst-type Programming First, Then Baseline Programming | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Baseline (Visit 1) | First Treatment / Programming Setting | 20 score on a scale |
| Experimental Burst-type Programming First, Then Baseline Programming | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Baseline (Visit 1) | Second Treatment / Programming Setting | 32 score on a scale |
Primary
Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Six Months (Visit 2)
This outcomes is the Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score in the Medication Off state and after burst-type DBS programming in the acute setting (after 30 minutes) at six 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 108. A higher score means a worse outcome. Note that the study arm titles refer to whether or not the patients were randomized to baseline programming or Burst-type programming at Visit 1. During this visit (Visit 2), all study subjects were to be evaluated in the medication-off state and then evaluated following 30 minutes of treatment with Burst-type programming. Treatment with baseline programming was not administered during this visit (Visit 2).
Time frame: 6 months
Population: No subjects were randomized to the arm that received baseline (standard of care) programming first, followed by experimental Burst-style programming (at Visit 1). Follow-up data at six months (Visit 2) were only available for one of the two patients randomized to first be treated with the experimental Burst-type programming at Visit 1. Additionally, data were not collected in the Medication Off state for the patient for whom there are follow-up data at six months (Visit 2).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental Burst-type Programming First, Then Baseline Programming | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Six Months (Visit 2) | Burst-type Programming | 25 score on a scale |
| Unknown | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Six Months (Visit 2) | Medication-Off and DBS-Off State | — score on a scale |
Primary
Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Twelve Months (Visit 3)
This outcomes is the Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Score in the Medication Off state and after burst-type DBS programming in the acute setting (after 30 minutes) at 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 108. A higher score means a worse outcome. Note that the study arm titles refer to whether or not the patients were randomized to baseline programming or Burst-type programming at Visit 1. During this visit (Visit 2), all study subjects were to be evaluated in the medication-off state and then evaluated following 30 minutes of treatment with Burst-type programming. Treatment with baseline programming was not administered during this visit (Visit 2).
Time frame: 12 months
Population: No subjects were randomized to the arm that received baseline (standard of care) programming first, followed by experimental Burst-style programming (at Visit 1). Follow-up data at 12 months were only available for one of the two patients randomized to first be treated with the experimental Burst-type programming at Visit 1. Additionally, data were not collected in the Medication Off state for the patient for whom there are follow-up data at six months (Visit 2).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental Burst-type Programming First, Then Baseline Programming | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Twelve Months (Visit 3) | Burst-type Programming | 26 score on a scale |
| Unknown | Unified Parkinson's Disease Rating Scale (UPDRS) v-III Motor Examination Scores at Twelve Months (Visit 3) | Medication-Off and DBS-Off State | — score on a scale |