Dual Frequency Stimulation in Parkinson's Disease

Study Overview
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Brief Summary
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Deep brain stimulation (DBS) in the dorsal region of the subthalamic nucleus (STN) is very effective for reducing motor symptoms of Parkinson's disease (PD). Modeling studies suggest that this therapy may result in current spread into the ventral STN, causing altered cognitive processes. As a result, current stimulation parameters often lead to worsening in verbal fluency, executive function, and, particularly, cognitive control. There is evidence suggesting that low frequency oscillatory activity occurs across brain circuits important in integrating information for cognition. Preclinical studies and human recording studies indicate these low frequency theta oscillations drive cognitive control during cognitive tasks. Thus, the purpose of this study is to determine the safety, tolerability, and efficacy of low frequency stimulation (LFS) of the ventral STN alongside standard high frequency stimulation (HFS) of the dorsal STN in patients with PD.

Official Title
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Dual Frequency, Dual Region Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Deep brain stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who are 18 years and older Individuals with idiopathic Parkinson's Disease who previously underwent implantation with the Boston Scientific VerciseTM DBS system Individuals who have been implanted with the Boston Scientific VerciseTM DBS system for at least 3 months Individuals diagnosed with advanced PD who had bilateral dorsal subthalamic nucleus DBS surgery, as standard of care for motor improvement, with distal contacts of the electrodes implanted into the ventral STN Exclusion Criteria: Individuals unable to provide consent and/or lack capacity to consent Individuals diagnosed with any cognitive or physical impairments that would limit their ability to participate in the cognitive testing Individuals who score below 15 on the Montreal Cognitive Assessment Test-Blind Individuals who score above 20 on the Center for Epidemiologic Studies Depression Scale Pregnant women (note: pregnant women are not candidates for DBS surgery), and prisoners Non-English speaking individuals. Cognitive tasks will only be conducted in English.

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sustained Dual Frequency, Dual Region, Stimulation<br> | Device: Deep brain stimulation<br>* Patients with idiopathic Parkinson's disease who have previously been implanted with the Boston Scientific VerciseTM DBS system for at least 3 months. These patients will already be receiving high-frequency dorsal STN stimulation as part of the standard of care for PD. Once patients have provided consent and are enrolled in this study, they will receive simultaneous low-frequency stimulation of the ventral STN to examine if there are any effects on cognitive performance.<br>* Other names: Boston Scientific Vercise DBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change from Baseline in Depression Scores on the Center for Epidemiologic Studies Depression Scale (CES-D) | The score of the CES-D will be compared across sessions and a score that rises above 20 (out of 60) will be considered positive for the development of depression. | Baseline, Week 2, Week 6, Month 3, and Month 6 | 
| Mean Change from Baseline in Impulsiveness Scores on the Barratt Impulsiveness Scale (BIS-11) | The score of the BIS-11 will be evaluated across sessions and elevated scores indicate greater impulsivity and risk-taking behavior. The scale involves 30 questions with values from 1-4. Overall scores range from 30-120. | Baseline, Week 2, Week 6, Month 3, and Month 6 | 
| Mean Change from Baseline in Neuropsychiatric Inventory (NPI) | The NPI assesses frequency, change in severity, and distress over 12 neuropsychiatric domains as evaluated by the caregiver. We will look for a significant score reduction in any domain of the NPI. | Baseline, Week 2, Week 6, Month 3, and Month 6 | 
| Mean Change from Baseline in Movement Scores on Part III of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | Part III of the MDS-UPDRS consists of 18 areas of motor assessments to assess severity of symptoms. Each score is rated in terms of severity from 0-4, with higher scores indicating higher severity of symptoms. A composite score will be evaluated for changes from baseline. | Baseline, Week 2, Week 6, Month 3, and Month 6 | 
| Mean Change from Baseline in Cognitive Performance Scores on the Montreal Cognitive Assessment - Blind (MoCA) | This will be collected via telephone calls. The MoCA-Blind has been validated for telephone administration. We will re-evaluate MoCA-Blind scores during telephone monitoring to assess any changes to cognitive ability. A total score of less than 15 out of a possible 22 indicates greater than mild cognitive impairment. | Baseline, Hour 24, Week 1, Month 1, Month 2, Month 4, and Month 5 | 
| Mean Change from Baseline in Depression Scores on the CES-D Short Version (CES-D-R10) | This will be collected via telephone calls. Patients will be given an unmarked form with questions and will be able to follow along the telephone conversation and answer each question (0-4 severity rating scale) for 10 questions focused on patient affect. A total score greater than 10 (out of 30) indicates the development of depression symptoms. | Baseline, Hour 24, Week 1, Month 1, Month 2, Month 4, and Month 5 | 
| Mean Change from Baseline in Motor and Non-Motor Aspects of Daily Living Scores on Parts I and II of the MDS-UPDRS | This will be collected via telephone calls. Patients will be asked questions relating to motor and non-motor aspects of daily living and to rate the severity of their symptoms on a scale from 0-4, with higher scores indicating higher severity of symptoms. We will assess for changes in the composite score from baseline. | Baseline, Hour 24, Week 1, Month 1, Month 2, Month 4, and Month 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change from Baseline in Decision-Making Scores on Probabilistic Gambling Task | A patient-specific measure of risk attitude during a gambling task. We will estimate indifference points (win probability at which risky choice is chosen 50% of the time) at each time point and compare to those points during baseline performance on the task. | Baseline, Minute 30, Week 2, Week 6, Month 3, and Month 6 | 
| Mean Change from Baseline in Inter-Temporal Choice Scores on a Temporal Discounting Task | A patient-specific measure of risk attitude during a temporal preferences task. We will examine the area under the curve of the empirical discount functions of 'larger later' rewards and 'smaller sooner' rewards. Smaller values indicate increased preference for smaller sooner over larger later rewards. Scores will be compared to baseline performance on the task. | Baseline, Minute 30, Week 2, Week 6, Month 3, and Month 6 | 
| Mean Change from Baseline in Verbal Fluency Scores on Word Generation Task | The average number of words generated in a 1-minute time frame. | Baseline, Minute 30, Week 2, Week 6, Month 3, and Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DBS, Deep Brain Stimulation, STN, Subthalamic Nucleus, Parkinson disease, Dual frequency, Dual region, DFDR