The Motor Network in Parkinson's Disease and Dystonia: Mechanisms of Therapy
- Conditions
- Parkinson DiseaseDystonia
- Interventions
- Device: Summit RC+S for MotorDiagnostic Test: 8-week pilot trial of Closed-loop vs. Open-loop StimulationDevice: Summit RC+S for Sleep
- Registration Number
- NCT03582891
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
This is an exploratory pilot study to identify neural correlates of specific motor signs in Parkinson's disease (PD) and dystonia, using a novel totally implanted neural interface that senses brain activity as well as delivering therapeutic stimulation. Parkinson's disease and isolated dystonia patients will be implanted unilaterally or bilaterally with a totally internalized bidirectional neural interface, Medtronic Summit RC+S.
This study includes three populations: ten PD patients undergoing deep brain stimulation in the subthalamic nucleus (STN), ten PD patients with a globus pallidus (GPi) target and five dystonia patients. All groups will test a variety of strategies for feedback-controlled deep brain stimulation, and all patients will undergo a blinded, small pilot clinical trial of closed-loop stimulation for thirty days.
- Detailed Description
In this project investigators will develop adaptive DBS algorithms based on cortical and subcortical signals using the RC+S. This bidirectional neural interface is rechargeable (for up to 9 years of use), and is capable of delivering therapeutic open-loop stimulation or closed-loop stimulation. Its sensing capability includes four simultaneous time series channels at up to 1000 Hz sampling rate. In addition the device can stream time series data, and calculate and stream spectral power within a preset bandwidth. Twenty patients with idiopathic PD and motor fluctuations, or medically intractable tremor, will be implanted with unilateral or bilateral RC+S devices, each connected to a standard quadripolar DBS lead implanted in STN or globus pallidus, and to a 4-contact paddle type electrode placed subdurally over sensorimotor cortex. The basal ganglia lead will be used for both stimulation and LFP recordings, while the cortical lead will be used only for recording ECoG potentials, not for stimulation.
Patients with motor fluctuations cycle between a hypokinetic state (too little movement) and a hyperkinetic state (excessive movement). During open-loop DBS, brain state continues to fluctuate between these states and stimulation may induce dyskinesia or inadequately relieve akinesia.
With the goal of maintaining motor function within a normal range away from these two extremes, investigators will develop and test stimulation algorithms that utilize putative markers of both kinetic states. Investigators will also study neural signals of sleep and test stimulation to support specific sleep stages. The basic strategy is to automatically adjust stimulation parameters until the physiological signature of abnormal function is minimized. First, investigators will prototype adaptive stimulation paradigms and briefly (2 hours) test them in clinic, using a "distributed" configuration (streaming to a computer). Then, investigators will embed these algorithms in RC+S to test chronic and fully closed-loop DBS in a small double-blinded clinical trial. Investigators will pay careful attention to the possibility of progressive reduction in stimulation currents over the course of the study, which could support the hypothesis that "adaptive stimulation" might make the brain progressively less dependent on the device. In quantifying DBS amplitude and comparing open loop with adaptive stimulation, an important parameter is the total electrical energy delivered (TEED). TEED is calculated by the following equation as suggested by Koss and colleagues (TEED1sec = ((voltage2 x frequency x pulsewidth)/impedance) x 1sec). This can be used as measure of the energy saved when stimulation is delivered in closed-loop mode relative to empiric open-loop stimulation.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 25
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Parkinson's Disease STN Target Summit RC+S for Motor Parkinson's disease patients implanted in STN Parkinson's disease patients GP Target Summit RC+S for Sleep Parkinson's disease patients implanted in Globus Pallidus Dystonia patients 8-week pilot trial of Closed-loop vs. Open-loop Stimulation Isolated dystonia patients Parkinson's Disease STN Target 8-week pilot trial of Closed-loop vs. Open-loop Stimulation Parkinson's disease patients implanted in STN Parkinson's Disease STN Target Summit RC+S for Sleep Parkinson's disease patients implanted in STN Dystonia patients Summit RC+S for Motor Isolated dystonia patients Parkinson's disease patients GP Target Summit RC+S for Motor Parkinson's disease patients implanted in Globus Pallidus Parkinson's disease patients GP Target 8-week pilot trial of Closed-loop vs. Open-loop Stimulation Parkinson's disease patients implanted in Globus Pallidus
- Primary Outcome Measures
Name Time Method Positive and Negative Affect Schedule (PANAS-SF) Through study completion, up to 4 years This is a standardized mood questionnaire
The Burke-Fahn-Marsden Dystonia Rating Scale-Movement aDBS testing compared to pre-operative baseline(Dystonia Patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. This scales evaluates dystonia in nine body areas, including eyes, mouth, speech and swallowing, neck, trunk, and right and left arm and leg. The maximal total score is 120 - a higher score means worsening symptoms. Investigators will compare the dystonia symptoms and functional disability during adaptive stimulation compared to preoperative baseline.
Toronto Western Spasmodic Torticollis Rating Scale during aDBS testing compared to pre-operative baseline (Dystonia Patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. This is a standardized scale to measure the severity, disability, and pain associated with cervical dystonia. The motor severity subscale consists of 10 items, with variable scaling and weighting. It also includes a disability scale with six items,and a pain scale with three items. The total score is the sum of each of the subscales. A higher score indicates greater disability.
Karolinska Sleepiness Scale Through study completion, up to 4 years This is a standardized scale for measuring sleepiness
Psychomotor vigilance task (PVT) Through study completion, up to 4 years This is a standardized behavioral task for measure alertness and attention
Duration of 'on' stimulation time without dyskinesia from motor diaries in adaptive compared to standard open loop stimulation. (Parkinson's disease patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. Duration of 'on' stimulation time without dyskinesia in adaptive compared to standard open loop stimulation determined from the patients' motor diaries. The self-report motor diary is a validated method to capture this information. Every half-hour, patients indicate in this diary which of 4 categories (on, on with troubling dyskinesia, off, or asleep) best reflected their predominant symptoms for the prior 30 minutes. Patients will complete this diary for 3 consecutive days. The total time spent in the 'on' state without troubling dyskinesia will then be summed and averaged over 3 days for all three conditions (baseline, open-loop stimulation and closed-loop stimulation).
- Secondary Outcome Measures
Name Time Method Patient Global Impression of Change (Dystonia Patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. Patient Global Impression of Changes measures the self-reported level of overall improvement (motor and non-motor symptoms) in a patient on a 1-7 scale. A one indicates no change and a 7 is the greatest level of improvement.
Schwab England scale in adaptive compared to standard open loop stimulation. (Parkinson's disease patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. This scale estimates the abilities of individuals living with Parkinson's Disease relative to a completely independent situation. Investigators will use it to compare the abilities of daily living in subjects during the open-loop and adaptive stimulation trial.
Hoehn and Yahr Staging in the medication 'on' state in adaptive compared to standard open loop stimulation. (Parkinson's disease patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. The Hoehn and Yahr scale are used to describe the progression of Parkinson's disease based upon the level of motor impairment. This scale only includes one score ranging from 1 to 5 where a higher score indicates a higher level of motor impairment. Investigators will compare the level of disease progression between the open-loop and adaptive stimulation conditions.
Patient's Global Impression of Change (PGIC) in adaptive compared to standard open loop stimulation. (Parkinson's disease patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. Patient Global Impression of Changes measures the self-reported level of overall improvement (motor and non-motor symptoms) in a patient on a 1-7 scale. A one indicates no change and a 7 is the greatest level of improvement.
Total Electric Energy Delivered (TEED) by the pulse generator in adaptive compared to standard open loop stimulation. (all patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. Investigators will compare the total charge delivered by the pulse generator between open-loop and adaptive stimulation to determine if there is a potential energy savings.
Short form 36 Quality of Life measure (Dystonia Patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. The SF-36 is a measure of self-reported health status which is scored on a 0-100 scale. The lower the score the more disability a patient experiences.
The Unified Parkinsons Disease Rating Scale (UPDRS) III scores off of medication in adaptive compared to standard open-loop stimulation. (Parkinson's disease patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. The UPDRS III is a motor rating scale. Investigators will compare the severity motor symptoms while the patient is off of Parkinsoniae (UPDRS) III scores off of medication in adaptive compared to standard open-loop stimulation. (Parkinson's disease patients)n medications in conventional (open-loop) versus adaptive (closed-loop) DBS.
The patient' quality of life report (PDQ-39) in adaptive compared to standard open loop stimulation. The PDQ39 yields a score between 0 to 100, where a higher score indicates more health problems. (Parkinson's disease patients) Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home. The PDQ 39 questionnaire has 39 questions to assess the patient's life quality including mobility, emotional state, and bodily comfort. Investigators will make a comparison of patients' life quality of life between open-loop and adaptive stimulation.
Resting state EEG Recording Through study completion, up to 4 years Resting state cortical power will be analyzed as a surrogate marker of alertness
Trial Locations
- Locations (1)
University of California at San Francisco
🇺🇸San Francisco, California, United States