Enhancing Gait Using Alternating-Frequency DBS in Parkinson Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess how alternating-frequency Deep Brain Stimulation (DBS) works to improve postural instability and gait, while also treating other motor symptoms of Parkinson Disease (PD).

Detailed Description
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Postural instability, gait impairment, and falls are among the greatest unmet needs in Parkinson disease (PD). A single fall can be catastrophic, and impairments that limit mobility lead to social isolation or depression, and adversely affect bone and cardiovascular health. Unfortunately, postural instability and gait disorders are refractory to current pharmacological and surgical treatments, including deep brain stimulation (DBS). This project will directly address this pressing need. We will recruit participants to perform a gait task, using a new, alternating DBS frequency paradigm, while body movements and neural signals are recorded. The findings will lead to improved therapies to address these symptoms in the future.

Official Title
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ENGAGE-PD: Enhancing Gait Using Alternating-Frequency DBS in Parkinson Disease

Conditions
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Parkinson Disease, Gait Disorders, Neurologic, Disease Progression, Subthalamic Nucleus, Accidental Fall, Deep Brain Stimulation

Intervention / Treatment
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* Device: High-Frequency-Only Stimulation
* Device: Low-Frequency-Only Stimulation
* Device: Alternating, 50 sec High-Frequency, 10 sec Low-Frequency Stimulation
* Device: Alternating, 50 sec High-Frequency, 50 sec Low-Frequency Stimulation
* Device: Alternating, 10 sec High-Frequency, 50 sec Low-Frequency Stimulation
* Device: Alternating, 10 sec High-Frequency, 10 sec Low-Frequency Stimulation
* Drug: OFF Dopaminergic Medication
* Drug: ON Dopaminergic Medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bilateral STN DBS for PD Medtronic Percept PC implanted DBS battery/pulse generator/recording system Presence of balance and/or walking impairment and/or freezing of gait Can walk without assistance, OFF meds, based on yes/no verbal response Exclusion Criteria: Severity of gait impairment should not require dependency to walker or cane Cannot tolerate monopolar stimulation at either of the two middle electrode contacts (prerequisite for the recording mode of the DBS) at high frequency (130 Hz) or low frequency (60 Hz). Concomitant conditions that may affect significantly the evaluation of balance or gait, including orthopedic, rheumatologic or other neurological diseases Contraindication to physical therapy Age < 21 Diagnosis of dementia Not agreeable to having video taken of entire research visit

Ages Eligible for Study
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Minimum Age: 21 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
Interventional Model Description: On a single day, participants will switch between six DBS frequency conditions. Gait and body kinematics will be monitored during these conditions. The order that participants experience the six conditions will be randomized, and participants will be blinded to the condition. In addition, the assessments will be performed OFF and then repeated ON medication.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alternating-Frequency DBS<br>In this single-arm study, all participants will receive all interventions in a crossover fashion. | Device: High-Frequency-Only Stimulation<br>* Control condition, constant high-frequency DBS stimulation (130Hz)<br>Device: Low-Frequency-Only Stimulation<br>* Experimental condition, constant low-frequency DBS stimulation (60 Hz)<br>Device: Alternating, 50 sec High-Frequency, 10 sec Low-Frequency Stimulation<br>* Experimental condition where stimulation frequency is changed from high (130Hz) to low (60Hz) frequency. The time interval for each frequency is 50 seconds for high, and 10 seconds for low, respectively.<br>Device: Alternating, 50 sec High-Frequency, 50 sec Low-Frequency Stimulation<br>* Experimental condition where stimulation frequency is changed from high (130Hz) to low (60Hz) frequency. The time interval for each frequency is 50 seconds for high, and 50 seconds for low, respectively.<br>Device: Alternating, 10 sec High-Frequency, 50 sec Low-Frequency Stimulation<br>* Experimental condition where stimulation frequency is changed from high (130Hz) to low (60Hz) frequency. The time interval for each frequency is 10 seconds for high, and 50 seconds for low, respectively.<br>Device: Alternating, 10 sec High-Frequency, 10 sec Low-Frequency Stimulation<br>* Experimental condition where stimulation frequency is changed from high (130Hz) to low (60Hz) frequency. The time interval for each frequency is 10 seconds for high, and 10 seconds for low, respectively.<br>Drug: OFF Dopaminergic Medication<br>* All six device interventions will be performed in medication OFF state<br>Drug: ON Dopaminergic Medication<br>* All six device interventions will be performed in medication ON state<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stride Time Coefficient of Variation | Marker of gait instability, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 
| Percentage of Time with Tremor Present | Marker of tremor severity, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 
| Tremor Amplitude | Marker of tremor severity, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Freezing Time | Marker of gait instability, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 
| Freezing Index | Marker of gait instability, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 
| Gait Velocity | Marker of bradykinesia, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 
| Step Cadence | Marker of bradykinesia, derived from kinematic recordings from body-worn wireless sensors. | During the intervention | 
| LFP and EEG power spectrum correlation with behavior and kinematics | Neural recordings (LFP = Local Field Potential and EEG = Electroencephalogram) from the DBS electrode and from EEG electrodes will be analyzed in the frequency domain. Assessed frequency bands will include delta, theta, alpha, beta, and gamma activity. These will be correlated with behavior and kinematic recordings to determine the neural correlates of gait instability and other parkinsonian symptoms. | During the intervention | 
| LFP and EEG connectivity correlation with behavior and kinematics | Neural recordings (LFP = Local Field Potential and EEG = Electroencephalogram) consist of multiple channels of simultaneously measured electrical activity. Connectivity is a measure of correlations between each pair of recorded and postprocessed channels, at each frequency band, over time. A machine learning algorithm will be trained to correlate the connectivity to behavior and kinematic recordings, to determine the neural correlates of gait instability and other parkinsonian symptoms. | During the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postural Instability, Gait Impairment, Freezing of Gait, Frequency, Low, Alternating, Variable, High, DBS