Closed Loop DBS Implanted RC+S Study

Study Overview
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Brief Summary
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This study involves patients who are already planning to have deep brain stimulation (DBS) surgery to treat the symptoms of severe Parkinson's Disease (PD). The study has two goals: to evaluate the effectiveness of implanting DBS electrodes in the two most common locations for DBS (subthalamic nucleus (STN), and globus pallidus interna (GPi)), instead of just one electrode, on each side of the brain; and to develop an adaptive DBS system using brain signals measured from these two electrodes.

Detailed Description
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The purpose of this study is a small, first in man, clinical feasibility trial for patients with severe Parkinson's Disease (PD), who are already clinically eligible for deep brain stimulation (DBS) with two goals: to compare efficacy from two common sites of DBS (subthalamic nucleus (STN), and globus pallidus interna (GPi)) through the implantation of dual DBS electrodes on each side of the brain; and to develop a closed loop DBS system using evoked and spontaneous potentials derived from these two electrodes. The study will involve bilateral dual DBS electrode placement in clinically standard locations (ie, STN and GPi) unilaterally or (more often) bilaterally, the placement of the RC+S Medtronic research implantable pulse generator (IPG), and a commitment to return for both extensive postoperative programming and testing to define clinical efficacy and separate research days to develop the closed loop approach. In addition, patients will undergo intraoperative research using temporary percutaneous extensions to the DBS electrode(s) and DBS lead cannula after implantation to confirm the electrode location and to identify what the signals will look like during later chronic recordings through the research IPG. The research RC+S IPG includes both ordinary DBS stimulation as well as a recording system that simultaneously measures the DBS local evoked potential (DLEP) and/or local field potential (LFP) responses from either the same or a second DBS electrode.

Official Title
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An Integrated Biomarker Approach to Personalized, Adaptive Deep Brain Stimulation in Parkinson Disease [Formerly: Scalar Closed-Loop STN/GPi DBS Based on Evoked and Spontaneous Potentials (Permanently Implanted Medtronic RC+S Studies)]

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: STN alone
* Device: GPi alone
* Device: STN + GPi
* Device: Closed-loop stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: able to give informed consent diagnosed with Parkinson's Disease and is considered a surgical candidate for DBS has medication-related side effects from levodopa (i.e., dyskinesias, on-off fluctuations) has off-on improvement with levodopa of at least 30% is available for follow-up visits for length of study Exclusion Criteria: is not safe surgical candidate for DBS has severe neurological injury or disease other than Parkinson's Disease has condition requiring repeated MRI scans has untreated, clinically significant depression has an electrical or electromagnetic implant had a prior thalamotomy or surgical ablation procedure has dementia interfering with ability to comply with study requirements or give informed consent abuses drugs or alcohol has a history of seizures has any metallic implants is pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Implanted RC+S<br>Implanted Medtronic RC+S IPG with dual DBS electrodes in STN and GPi. DBS stimulation will be administered to: 1) STN alone, 2) GPi alone, 3) cooperative STN + GPi, and 4) adaptive, closed-loop stimulation of STN and/or GPi. | Device: STN alone<br>* DBS stimulation of STN alone<br>Device: GPi alone<br>* DBS stimulation of GPi alone<br>Device: STN + GPi<br>* cooperative DBS stimulation of STN and GPi sites<br>Device: Closed-loop stimulation<br>* adaptive DBS stimulation of STN and/or GPi sites<br>|

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) score: on medication, on stimulation at 12 months after IPG implant. | Change in UPDRS score for subject from baseline (pre-surgery) on medication state to on medication and on stimulation state at 12 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. The scores from four subscales (1. Mentation, Behavior and Mood, 2. Activities of Daily Living, 3. Motor Examination, and 4. Complications of Therapy) are summed to determine the total UPDRS score. Total scores range from 0 (no disability) to 199 (total disability). | baseline and 12 months after IPG implant | 
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) score: on medication, on stimulation at 24 months after IPG implant. | Change in UPDRS score for subject from baseline (pre-surgery) on medication state to on medication and on stimulation state at 24 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. The scores from four subscales (1. Mentation, Behavior and Mood, 2. Activities of Daily Living, 3. Motor Examination, and 4. Complications of Therapy) are summed to determine the total UPDRS score. Total scores range from 0 (no disability) to 199 (total disability). | baseline and 24 months after IPG implant | 
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) score: on medication, on stimulation at 48 months after IPG implant. | Change in UPDRS score for subject from baseline (pre-surgery) on medication state to on medication and on stimulation state at 48 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. The scores from four subscales (1. Mentation, Behavior and Mood, 2. Activities of Daily Living, 3. Motor Examination, and 4. Complications of Therapy) are summed to determine the total UPDRS score. Total scores range from 0 (no disability) to 199 (total disability). | baseline and 48 months after IPG implant | 
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) score: on medication, on stimulation at 72 months after IPG implant. | Change in UPDRS score for subject from baseline (pre-surgery) on medication state to on medication and on stimulation state at 72 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. The scores from four subscales (1. Mentation, Behavior and Mood, 2. Activities of Daily Living, 3. Motor Examination, and 4. Complications of Therapy) are summed to determine the total UPDRS score. Total scores range from 0 (no disability) to 199 (total disability). | baseline and 72 months after IPG implant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's Disease Rating Scale, subscale III: Motor Evaluation (UPDRS-III) score: off medication, on stimulation at 12 months after IPG implant. | Change in UPDRS-III (Motor Evaluation) score from baseline (pre-surgery) off medication state to off medication and on stimulation state at 12 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. Subscale III, Motor Examination, scores range from 0 (no disability) to 108 (total disability). | baseline and 12 months after IPG implant | 
| Change in Unified Parkinson's Disease Rating Scale, subscale III: Motor Evaluation (UPDRS-III) score: off medication, on stimulation at 24 months after IPG implant. | Change in UPDRS-III (Motor Evaluation) score from baseline (pre-surgery) off medication state to off medication and on stimulation state at 24 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. Subscale III, Motor Examination, scores range from 0 (no disability) to 108 (total disability). | baseline and 24 months after IPG implant | 
| Change in Unified Parkinson's Disease Rating Scale, subscale III: Motor Evaluation (UPDRS-III) score: off medication, on stimulation at 48 months after IPG implant. | Change in UPDRS-III (Motor Evaluation) score from baseline (pre-surgery) off medication state to off medication and on stimulation state at 48 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. Subscale III, Motor Examination, scores range from 0 (no disability) to 108 (total disability). | baseline and 48 months after IPG implant | 
| Change in Unified Parkinson's Disease Rating Scale, subscale III: Motor Evaluation (UPDRS-III) score: off medication, on stimulation at 72 months after IPG implant. | Change in UPDRS-III (Motor Evaluation) score from baseline (pre-surgery) off medication state to off medication and on stimulation state at 72 months after IPG implant. The UPDRS is a scale to measure the degree of a patient's disability due to Parkinson's Disease. Subscale III, Motor Examination, scores range from 0 (no disability) to 108 (total disability). | baseline and 72 months after IPG implant | 
| Change in percentage of waking hours with good on time at 12 months after IPG implant. | Change in percentage of waking hours subject experienced on time without troubling dyskinesias, based on 3-day motor diary, compared to pre-surgery baseline. | baseline and 12 months after IPG implant | 
| Change in percentage of waking hours with good on time at 24 months after IPG implant. | Change in percentage of waking hours subject experienced on time without troubling dyskinesias, based on 3-day motor diary, compared to pre-surgery baseline. | baseline and 24 months after IPG implant | 
| Change in percentage of waking hours with good on time at 48 months after IPG implant. | Change in percentage of waking hours subject experienced on time without troubling dyskinesias, based on 3-day motor diary, compared to pre-surgery baseline. | baseline and 48 months after IPG implant | 
| Change in percentage of waking hours with good on time at 72 months after IPG implant. | Change in percentage of waking hours subject experienced on time without troubling dyskinesias, based on 3-day motor diary, compared to pre-surgery baseline. | baseline and 72 months after IPG implant | 
| Change in Parkinson's Disease Questionnaire-39 (PDQ-39) patient satisfaction score at 12 months after IPG implant. | Change in PDQ-39 score compared to pre-surgery baseline. The PDQ-39 is a 39-item self-reporting questionnaire to assess the impact of Parkinson's Disease on quality of life. The PDQ-39 is divided into 8 dimensions (1. Mobility, 2. Activities of Daily Life, 3. Emotional Well-being, 4. Stigma, 5. Social Support, 6. Cognition, 7. Communication, and 8. Bodily Discomfort). The total score is the sum of the dimension total scores divided by 8. Scores range from 0 (better quality of life) to 100 (worse quality of life). | baseline and 12 months after IPG implant | 
| Change in Parkinson's Disease Questionnaire-39 (PDQ-39) patient satisfaction score at 24 months after IPG implant. | Change in PDQ-39 score compared to pre-surgery baseline. The PDQ-39 is a 39-item self-reporting questionnaire to assess the impact of Parkinson's Disease on quality of life. The PDQ-39 is divided into 8 dimensions (1. Mobility, 2. Activities of Daily Life, 3. Emotional Well-being, 4. Stigma, 5. Social Support, 6. Cognition, 7. Communication, and 8. Bodily Discomfort). The total score is the sum of the dimension total scores divided by 8. Scores range from 0 (better quality of life) to 100 (worse quality of life). | baseline and 24 months after IPG implant | 
| Change in Parkinson's Disease Questionnaire-39 (PDQ-39) patient satisfaction score at 48 months after IPG implant. | Change in PDQ-39 score compared to pre-surgery baseline. The PDQ-39 is a 39-item self-reporting questionnaire to assess the impact of Parkinson's Disease on quality of life. The PDQ-39 is divided into 8 dimensions (1. Mobility, 2. Activities of Daily Life, 3. Emotional Well-being, 4. Stigma, 5. Social Support, 6. Cognition, 7. Communication, and 8. Bodily Discomfort). The total score is the sum of the dimension total scores divided by 8. Scores range from 0 (better quality of life) to 100 (worse quality of life). | baseline and 48 months after IPG implant | 
| Change in Parkinson's Disease Questionnaire-39 (PDQ-39) patient satisfaction score at 72 months after IPG implant. | Change in PDQ-39 score compared to pre-surgery baseline. The PDQ-39 is a 39-item self-reporting questionnaire to assess the impact of Parkinson's Disease on quality of life. The PDQ-39 is divided into 8 dimensions (1. Mobility, 2. Activities of Daily Life, 3. Emotional Well-being, 4. Stigma, 5. Social Support, 6. Cognition, 7. Communication, and 8. Bodily Discomfort). The total score is the sum of the dimension total scores divided by 8. Scores range from 0 (better quality of life) to 100 (worse quality of life). | baseline and 72 months after IPG implant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Brain Stimulation