Parkinson's Disease (PD)
Conditions
Keywords
neuromodulation, closed-loop deep brain stimulation, gait impairments, motor learning, parkinson's disease
Brief summary
This is a single-center clinical study aiming to improve gait functions in patients with Parkinson's Disease (PD) by using adaptive neurostimulation to the pallidum. The investigators will use a bidirectional deep brain stimulation device with sensing and stimulation capabilities to 1) identify neural biomarkers to detect the onset of walking by recording neural activities from the motor cortical areas and the globus pallidus, 2) understand the impacts of changes in DBS parameters on gait kinematics and optimize setting parameters for enhancing walking performance, 3) develop a movement state-dependent adaptive deep brain stimulation (DBS) paradigm to automatically switch stimulation settings according to different movement states (i.e., walking vs non-walking). The proposed therapy will deliver personalized neurostimulation based on individual physiological biomarkers to enhance gait function in patients with PD. 6 patients with idiopathic Parkinson's disease who have already been implanted with the Medtronic Summit RC+S device will be enrolled in this study.
Detailed description
This study will allow the investigators to evaluate the efficacy of a movement state-dependent adaptive deep brain stimulation paradigm to treat gait dysfunction in individuals with Parkinson's disease (PD). While current DBS therapy improves the appendicular symptoms of PD, such as tremor and bradykinesia, it is less effective for advanced gait symptoms, which manifest as hypokinetic gait patterns, increased gait variability, asymmetry, and disturbed balance. These symptoms are debilitating and represent a major source of morbidity for patients with PD. Studies have suggested that while conventional high-frequency stimulation settings are good at treating appendicular symptoms, they may not be as effective for axial symptoms such as gait disorders. Modulating stimulation parameters, by using lower frequencies, for instance, has been shown to improve gait kinematics such as symmetry and rhythmicity. However, these settings are less effective for other symptoms and therefore come at the expense of appendicular symptom control. The overall objective of this study is to identify personalized electrophysiological signatures of movement state and gait-optimized stimulation parameters in PD patients to enable adaptive control algorithms that automatically switch from identified 'gait-optimized' settings during walking to 'other PD symptom-optimized' settings during non-walking. This is a small, double-blinded trial, six patients with idiopathic PD and motor fluctuations who have already been implanted with the RC+S devices. The investigators will compare the overall efficacy of closed-loop (adaptive DBS) and open-loop (continuous clinical DBS) paradigms in terms of behavioral performance improvements. During this chronic movement state-dependent adaptive DBS phase, adaptive DBS and open-loop stimulation settings will be randomized for 7-day periods, and motor and gait-related measurements will be obtained from wearable devices that track movement kinematics. Patients will participate in daily, if possible, motor and gait tasks at home and are asked to fill out motor diary questionnaires to share their feedback from both motor and non-motor perspectives. The investigators expect to successfully develop a prototype movement state-dependent adaptive DBS algorithm. They hypothesize that the embedded closed-loop, movement state-dependent adaptive DBS paradigm will improve gait function compared to the conventional open-loop approach, in which stimulation parameters remain constant, while maintaining the standard therapeutic benefits of DBS.
Interventions
DEVICESummit RC+S
Participants receive gait-optimized stimulation settings while walking and Parkinson's disease symptom-optimized settings during non-walking periods.
Sponsors
Doris Wang, MD, PhD
Michael J. Fox Foundation for Parkinson's Research
Burroughs Wellcome
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
In a small, double-blinded trial, the investigators will compare the overall efficacy of closed-loop and open-loop paradigms in terms of behavioral performance improvements in subject-reported metrics and validated measurements from wearable devices. During the long-term movement state-dependent adaptive DBS (aDBS) phase, aDBS and open-loop constant stimulation settings will be randomized for 7-day periods, and motor and gait-related measurements will be obtained from wearable devices that track movement kinematics. At the end of each 7-day block, the research team will administer clinical tests, including the Montreal Cognitive Assessment (MoCA), Unified Parkinson's Disease Rating Scale (UPDRS) III, and the Mini Balance Evaluation Systems Test (Mini-BESTest).
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Ability to give informed consent for the study * Subjects implanted with Summit RC+S investigational DBS system. * Absence of significant cognitive impairment (score of 21 or greater on the Montreal Cognitive Assessment (MoCA) * Signed informed consent * Age 21-75 * Diagnosis of idiopathic PD with duration of motor symptoms for 3 years or greater * Patient has undergone appropriate therapy with oral medications with inadequate relief as determined by a movement disorders neurologist. * UPDRS-III score off medication between 20 and 80 and an improvement of at least 30% in the baseline UPDRS-III on medication score, compared to the baseline off-medication score, and motor fluctuations with at least 2 hours per day of on time without dyskinesia or with non-bothersome dyskinesia. OR Patients with tremor-dominant PD (a tremor score of at least 2 on a UPDRS-III sub-score for tremor), treatment resistant, with significant functional disability despite maximal medical management * Patients with gait impairments: slowed gait, shuffling steps, postural instability, or freezing of gait off medication.
Exclusion criteria
* Inability to comply with study procedures * Patients who cannot walk (wheelchair bound)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mini Balance Evaluation Systems Test (Mini-BESTest) Scores | after each 7 day block | Change in Mini-BESTest scores, which is a clinical balance evaluations systems test. The score range is 0-2 with higher scores indicating higher levels of physical functioning. |
| Change in Gait | 14 day long-term testing period | Change in gait measurements using the wearable devices (i.e., ankle wristband Rover and STAT-ON Holter) |
| Change in Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores | after each 7 day block | Change in MDS-UPDRS III score. The scale consists of 18 items that are each scored 0 to 3, making the total score out of 72 points, with higher scores indicating higher impairment. |
| Change in Stride Length | 14 day long-term testing period | Change in stride length measured by Rover (a gait measurement device) and STAT-ON (a Parkinson's disease motor symptoms measurement device) with closed-loop compared to open-loop deep brain stimulation (DBS). Stride length measured in meters. |
| Change in Stride Time | 14 day long-term testing period | Change in stride time measured by Rover (a gait measurement device) and STAT-ON (a Parkinson's disease motor symptoms measurement device) with closed-loop compared to open-loop deep brain stimulation (DBS). Stride time measured in seconds. |
| Change in Double Support Time | 14 day long-term testing period | Change in stride time measured by Rover (a gait measurement device). Each gait cycle consists of two phases, where both feet are in contact with the ground, called Double Support. Double support time will be measured in seconds (i.e. amount of time both feet are in contact with the ground). |
| Change in number of freezes | 14 day long-term testing period | Change in number of freezes measured by STAT-ON (a Parkinson's disease motor symptoms measurement device) with closed-loop compared to open-loop deep brain stimulation (DBS). |
| Change in number of falls | 14 day long-term testing period | Change in number of falls measured by STAT-ON (a Parkinson's disease motor symptoms measurement device) with closed-loop compared to open-loop deep brain stimulation (DBS). |
| Change in Activities-Specific Balance Confidence (ABC) Scale | once per day during 14 day long-term testing period | Change in ABC Scale, which collects measures of confidence in performing various ambulatory activities without falling or experiencing a sense of unsteadiness. The score range is 0-100 with higher scores indicating higher levels of physical functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montreal Cognitive Assessment (MoCA) scores | after each 7 day block | Change in MoCA score. The scale consists of 30 1-point questions testing short term memory, visuospatial abilities, executive functions, attention, concentration, working memory, language, and orientation to time and place, with scores lower than 26 indicating possible cognitive impairment. |
| Changes in Parkinson's Disease (PD) Symptoms Questionnaire | once per day during 14 day long-term testing period | Changes in responses to a questionnaire that collects information about PD symptoms, balance, walking, falls, and freezing of gait. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDoris Wang, MD, PhD
University of California, San Francisco
Outcome results
None listed