- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04675398
Adaptive Deep Brain Stimulation to Improve Motor and Gait Functions in Parkinson's Disease
Adaptive Cortical and Subcortical Brain Stimulation to Improve Motor Behaviors and Gait in Parkinson's Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study will allow the investigators to evaluate the efficacy of an adaptive stimulation paradigm in deep brain stimulation (DBS) to treat motor-related behaviours and motor skill learning in Parkinson's disease (PD). Parkinson's disease patients will be implanted unilaterally or bilaterally with a totally internalized bidirectional neural interface, Medtronic Summit RC+S.
While current DBS therapy improves motor symptoms of PD, it does not address problems with acquiring additional motor skills (i.e. adapting gait patterns to avoid falls)) in PD, therefore, limiting benefits of physical rehabilitation programs aimed at improving mobility. Motor skill learning is critical in acquiring any new behaviors related to motor function. The overall objective is to identify personalized electrophysiological signatures of motor skill learning in PD patients and use adaptive control algorithms to enhance these signatures. The study will discover new ways to rehabilitate the disease brain circuits using adaptive neuromodulation.
In a small, double-blinded trial, ten patients with idiopathic PD and motor fluctuations will be implanted with unilateral or bilateral RC+S devices, each connected to a standard quadripolar DBS lead implanted in the basal ganglia, along with a 4-contact paddle type electrode placed subdurally over the motor cortex. The investigators will compare the overall efficacy of closed-loop and open-loop paradigms in terms of behavioral performance improvements in validated motor skill learning tasks and measurements from wearable devices. During this chronic adaptive DBS phase, adaptive DBS and open-loop stimulation settings will be randomized for 30-day periods and motor skill and gait related measurements will be obtained from a combination of computerized motor tasks and wearable devices that track movement kinematics. Patients will participate in daily, if possible, motor learning and gait tasks at home with triggered stimulation settings and recordings.
The investigators expect to successfully develop a prototype adaptive DBS algorithm based on cortical and / or basal ganglia LFPs (local field potentials). The investigators hypothesize that an adaptive paradigm will provide improvements in motor skilled learning compared to the conventional, open-loop paradigm, in which stimulation parameters remain constant until changed by the patient or clinician using an external programmer.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
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California
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San Francisco, California, United States, 94134
- UCSF
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Ability to give informed consent for the study
- Movement disorder symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
- Patient has requested surgical intervention with deep brain stimulation for their disorder
- No movement -elated abnormalities that suggest an alternative diagnosis or contraindicate surgery
- Absence of significant cognitive impairment (score of 21 or greater on the Montreal Cognitive Assessment (MoCA),
- Signed informed consent
- Ability to comply with study follow-up visits for brain recording, testing of adaptive stimulation, and clinical assessment.
- 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.
- Ability of patient and/or caregivers to recharge the system evaluated by all clinicians and study personnel.
- Geographical proximity and/or ability to travel to study sites for patient to receive re-programming via investigational devices (e.g. Summit Research Laboratory Programmer).
Exclusion Criteria:
- Coagulopathy, anticoagulant medications, uncontrolled hypertension, history of seizures, heart disease, or other medical conditions considered to place the patient at elevated risk for surgical complications
- Evidence of a psychogenic movement disorder: Motor symptoms that remit with suggestion or "while unobserved", symptoms that are inconsistent over time or incongruent with clinical condition, plus other manifestation such as "false" signs, multiple somatizations, or obvious psychiatric disturbance.
- Pregnancy: all women of child bearing potential will have a negative urine pregnancy test prior to undergoing their surgical procedure.
- Significant untreated depression (BDI-II score >20). History of suicidal attempt or active suicidal ideation (Yes to #2-5 on C-SSRS)
- Any personality or mood symptoms that study personnel believe will interfere with study requirements.
- Subjects who require electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS) or diathermy
- Implanted stimulation systems such as; cochlear implant, pacemaker, defibrillator, or neurostimulator
- Previous cranial surgery
- Drug or alcohol abuse
- Meets criteria for Parkinson's disease with mild cognitive impairment (PD-MCI). These criteria are: performance of more than two standard deviations below appropriate norms, for tests from two or more of these five cognitive domains: attention, executive function, language, memory, and visuospatial tests.
- Known allergies to the implantable device components including titanium, polyurethane, silicone, and nylon.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Open-loop deep brain stimulation
Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving open-loop deep brain stimulation.
|
Using the RC+S pulse generator, patients receive clinically-optimized open loop DBS stimulation to the pallidum.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation at random time points.
These random stimulation times will in total equal the total amount of time of active movement.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of contralateral limb movement (e.g.
left brain stimulation during right leg/arm movement).
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of no movement for the contralateral limb (e.g.
left brain stimulation while right leg/arm is not moving).
Other Names:
|
Active Comparator: Randomized deep brain stimulation
Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation at random time points.
|
Using the RC+S pulse generator, patients receive clinically-optimized open loop DBS stimulation to the pallidum.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation at random time points.
These random stimulation times will in total equal the total amount of time of active movement.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of contralateral limb movement (e.g.
left brain stimulation during right leg/arm movement).
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of no movement for the contralateral limb (e.g.
left brain stimulation while right leg/arm is not moving).
Other Names:
|
Active Comparator: Deep brain stimulation during contralateral limb movement
Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation during time of contralateral limb movement.
|
Using the RC+S pulse generator, patients receive clinically-optimized open loop DBS stimulation to the pallidum.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation at random time points.
These random stimulation times will in total equal the total amount of time of active movement.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of contralateral limb movement (e.g.
left brain stimulation during right leg/arm movement).
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of no movement for the contralateral limb (e.g.
left brain stimulation while right leg/arm is not moving).
Other Names:
|
Active Comparator: Deep brain stimulation during contralateral limb rest
Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation during time of no movement for contralateral limb.
|
Using the RC+S pulse generator, patients receive clinically-optimized open loop DBS stimulation to the pallidum.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation at random time points.
These random stimulation times will in total equal the total amount of time of active movement.
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of contralateral limb movement (e.g.
left brain stimulation during right leg/arm movement).
Other Names:
Using the RC+S pulse generator, the patients will receive closed-loop stimulation during time of no movement for the contralateral limb (e.g.
left brain stimulation while right leg/arm is not moving).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in motor learning task completion with closed-loop compared to open-loop deep brain stimulation (DBS)
Time Frame: Baseline and 2 years
|
Change in percentage of motor learning task trials that were completed with closed-loop compared to open-loop deep brain stimulation (DBS).
The task is made up of 840 trials, completion will be measured by percent of trials completed (e.g.
750/840 trials completed would be 89%).
The task has a built in function which logs completed trials in a CSV document.
|
Baseline and 2 years
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Change in motor learning task reaction times with closed-loop compared to open-loop deep brain stimulation (DBS)
Time Frame: Baseline and 2 years
|
Change in gait sequence motor learning task reaction times (measured in milliseconds) with closed-loop compared to open-loop deep brain stimulation (DBS).
|
Baseline and 2 years
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Change in motor learning task mean accuracy with closed-loop compared to open-loop deep brain stimulation (DBS).
Time Frame: Baseline and 2 years
|
Change in motor learning task mean accuracy with closed-loop compared to open-loop deep brain stimulation (DBS).
Accuracy will be measured as a percent using the tasks proprietary output log which records which trials out of the 840 total trials were target hits (i.e.
correct trials).
Mean accuracy will be calculated by taking the average of each patient's accuracy score across all attempts of the task done by said patient.
|
Baseline and 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Gait
Time Frame: Baseline and 2 years
|
Change in gait measurements using the 10-meter walk timed test.
The 10-Meter Walk Test (10MWT) is a performance measure used to assess walking speed in meters per second over a short distance of 10 meters.
It is employed to determine functional mobility and gait.
The gait speed is used as the outcome by which to compare change in performance capacity.
Lower times indicate higher levels of physical functioning.
|
Baseline and 2 years
|
Change in Balance
Time Frame: Baseline and 2 years
|
Change in balance measurements using: Mini-Best Test: Clinical balance assessment tool. The score range is 0-2 with high score indicating higher levels of physical functioning. Activities-Specific Balance Confidence Scale (ABC): 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. |
Baseline and 2 years
|
Change in MDS-UPDRS III scores
Time Frame: Baseline and 2 years
|
Change in Movement Disorders Society Unified Parkinson Disease Rating Scale (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.
|
Baseline and 2 years
|
Change in NIHTB Cognition Battery Test
Time Frame: Baseline and 2 years
|
Change in National Institute of Health Toolbox (NIHTB) Cognition battery test (during adaptive stimulation compared to open loop stimulation).
A score known as a theta score is calculated for each participant; it represents the relative overall ability or performance of the participant.
The theta score is converted to a Computed Score which ranges from roughly 0 to 2000 depending on the age-adjusted averages, with higher scores indicating higher levels of cognitive functioning.
|
Baseline and 2 years
|
Change in Five-Times Sit to Stand Test Results
Time Frame: Baseline and 2 years
|
Five-Times Sit to Stand Test: Assesses functional lower extremity strength, transitional movements, balance, and fall risk in older adults.
Scoring based on amount of time a patient is able to transfer from a seated to a standing position and back to sitting five times, with lower times indicating higher levels of physical functioning.
|
Baseline and 2 years
|
Change in Stride Length
Time Frame: Baseline and 2 years
|
Change in stride length measured by Rover (a gait measurement device) and Xsens (a kinematic measurement device) with closed-loop compared to open-loop deep brain stimulation (DBS).
Stride length is measured in meters.
|
Baseline and 2 years
|
Change in Stride Time
Time Frame: Baseline and 2 years
|
Change in stride time measured by Rover (a gait measurement device) and Xsens (a kinematic measurement device) with closed-loop compared to open-loop deep brain stimulation (DBS).
Stride time is measured in seconds.
|
Baseline and 2 years
|
Change in double support time
Time Frame: Baseline and 2 years
|
Change in double support 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).
|
Baseline and 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Doris Wang, MD, PhD, University of California, San Francisco
Publications and helpful links
General Publications
- Swann NC, de Hemptinne C, Miocinovic S, Qasim S, Ostrem JL, Galifianakis NB, Luciano MS, Wang SS, Ziman N, Taylor R, Starr PA. Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease. J Neurosurg. 2018 Feb;128(2):605-616. doi: 10.3171/2016.11.JNS161162. Epub 2017 Apr 14.
- Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M, Foltynie T, Limousin P, Ashkan K, FitzGerald J, Green AL, Aziz TZ, Brown P. Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 2013 Sep;74(3):449-57. doi: 10.1002/ana.23951. Epub 2013 Jul 12.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18649
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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