Bilateral Closed Loop Deep Brain Stimulation for Freezing of Gait Using Neural and Kinematic Feedback

Study Overview
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Brief Summary
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Deep Brain Stimulation of the subthalamic nucleus (STN) has become a standard of care, FDA-approved treatment for Parkinson's disease, with stimulation delivered at a constant amplitude and voltage, operating in an open-loop fashion that does not respond to a patient's current state. Although gait deficits and freezing of gait may initially respond to continuous open-loop deep brain stimulation (olDBS) and medication, the symptoms often recur over time. The episodic and predictable nature of FOG makes it well suited for adaptive DBS (aDBS) and a device that overcomes the limitations of traditional high frequency olDBS and is capable of adapting therapy either in the frequency or intensity domain transiently to treat FOG while also treating other PD signs such as tremor and bradykinesia. The purpose of this study is to determine the feasibility of an adaptive DBS system, that responds to patient-specific neural and kinematic variables with customized DBS parameters.

Official Title
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Bilateral Closed Loop Deep Brain Stimulation for Freezing of Gait Using Neural and Kinematic Feedback

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Open Loop DBS
* Device: Adaptive (Closed Loop) DBS
* Device: Intermittent Open Loop DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically-established PD Meets criteria for STN DBS eligibility as part of patient's standard medical care or already implanted in the STN with Percept(TM) PC The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors. Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS. Age > 18 Freezing of gait questionnaire (FOG-Q) score ≥ 1 and/or gait sub-score (Item 3.10) of MDS- UPDRS III ≥ 1 Greater than or equal to 1.2 microVp between 8-35 Hz on either the LSTN or RSTN (Percept (TM) PC cohort only) Exclusion Criteria: Dementia Untreated psychiatric disease Hoehn and Yahr stage 5 on or off medication (non-ambulatory) Age > 80 Major surgical morbidities such as severe hypertension, coagulopathy and certain metabolic conditions that might increase the risk of hemorrhage or other surgical complications Presence of a cardiac pacemaker/defibrillator Inability to understand/sign consent Requires rTMS, ECT, MRI (Summit(R) RC+S cohort only), or diathermy Are pregnant or lactating Has a cranial metallic implant History of seizures or epilepsy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will have either the Percept PC system, or Summit RC+S system from Medtronic PLC implanted.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Device: Summit RC+S<br>Open Loop DBS: Standard DBS therapy at a constant frequency and voltage Adaptive (Closed Loop) DBS: DBS that responds to neural or kinematic features of patient's current state Intermittent Open Loop DBS: Control for aDBS - DBS intensity or frequency changes in a manner that mimics aDBS but is pre-determined and open loop rather than being responsive to neural or kinematic signals. | Device: Open Loop DBS<br>* Standard DBS therapy at a constant frequency and voltage<br>Device: Adaptive (Closed Loop) DBS<br>* DBS that responds to neural (Percept PC and Summit RC+S) or kinematic (Summit RC+S) features of patient's current state<br>Device: Intermittent Open Loop DBS<br>* Control for aDBS - DBS intensity or frequency changes in a manner that mimics aDBS but is pre-determined and open loop rather than being responsive to neural or kinematic signals.<br>|
| Experimental: Device: Percept PC<br>Open Loop DBS: Standard DBS therapy at a constant frequency and voltage Adaptive (Closed Loop) DBS: DBS that responds to neural features of patient's current state | Device: Open Loop DBS<br>* Standard DBS therapy at a constant frequency and voltage<br>Device: Adaptive (Closed Loop) DBS<br>* DBS that responds to neural (Percept PC and Summit RC+S) or kinematic (Summit RC+S) features of patient's current state<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to Stimulation Condition | A Customized Adverse Events and Tolerability Questionnaire will measure the absence/presence and frequency of paresthesias, and muscle twitching relative to each stimulation condition | 3 Months | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to quality of life | The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, and IV will: (I) Evaluate mentation, behavior, and mood (II) Evaluate a patient's activities of daily life (IV) Measure the presence/severity of dyskinesias and other complications of therapy over time | 3 Months | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to speech | The Speech Intelligibility Test (SIT) will measure changes in speech related to each stimulation condition. | 6 Months | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] related to gait | The Freezing of Gait Questionnaire (FOG-Q) will be used to record changes in gait over time | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gait Parameters: Arrhythmicity | Variability in stride time during a gait task | Collected up to 10 days every 3 months | 
| Gait Parameters: Mean Shank Angular Velocity | Average of the peak shank angular velocities of every stride during the gait task | Collected up to 10 days every 3 months | 
| Gait Parameters: Mean Gait Cycle Time | Average length of time of each stride during a gait task | Collected up to 10 days every 3 months | 
| Percent Time Freezing | The percentage of the gait task was a participant frozen | Collected up to 10 days every 3 months | 
| The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | Portion of the scale assesses the motor signs of PD. Each item is scored on a scale from 0 (normal) to 4 (severe), with the total possible score ranging from 0 to 132. | Collected up to 10 days every 3 months |