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

Sponsor

The Cleveland Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT05022147

Collaborator

(none)

Enrollment

Location

Arm

9.1

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease Gait Disorders, Neurologic Disease Progression Subthalamic Nucleus Accidental Fall Deep Brain Stimulation	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	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Masking Description:

There is only one arm in the study. Participants will be masked to which device intervention is active, but they will not be masked to the medication state.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 4, 2021

Anticipated Primary Completion Date :

Jul 8, 2022

Anticipated Study Completion Date :

Jul 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alternating-Frequency DBS In this single-arm study, all participants will receive all interventions in a crossover fashion.	Device: High-Frequency-Only Stimulation Control condition, constant high-frequency DBS stimulation (130Hz) Device: Low-Frequency-Only Stimulation Experimental condition, constant low-frequency DBS stimulation (60 Hz) Device: Alternating, 50 sec High-Frequency, 10 sec Low-Frequency Stimulation 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. Device: Alternating, 50 sec High-Frequency, 50 sec Low-Frequency Stimulation 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. Device: Alternating, 10 sec High-Frequency, 50 sec Low-Frequency Stimulation 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. Device: Alternating, 10 sec High-Frequency, 10 sec Low-Frequency Stimulation 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. Drug: OFF Dopaminergic Medication All six device interventions will be performed in medication OFF state Drug: ON Dopaminergic Medication All six device interventions will be performed in medication ON state

Arm

Intervention/Treatment

Experimental: Alternating-Frequency DBS

In this single-arm study, all participants will receive all interventions in a crossover fashion.

Device: High-Frequency-Only Stimulation

Control condition, constant high-frequency DBS stimulation (130Hz)

Device: Low-Frequency-Only Stimulation

Experimental condition, constant low-frequency DBS stimulation (60 Hz)

Device: Alternating, 50 sec High-Frequency, 10 sec Low-Frequency Stimulation

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.

Device: Alternating, 50 sec High-Frequency, 50 sec Low-Frequency Stimulation

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.

Device: Alternating, 10 sec High-Frequency, 50 sec Low-Frequency Stimulation

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.

Device: Alternating, 10 sec High-Frequency, 10 sec Low-Frequency Stimulation

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.

Drug: OFF Dopaminergic Medication

All six device interventions will be performed in medication OFF state

Drug: ON Dopaminergic Medication

All six device interventions will be performed in medication ON state

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Total Freezing Time [During the intervention]
Marker of gait instability, derived from kinematic recordings from body-worn wireless sensors.
Freezing Index [During the intervention]
Marker of gait instability, derived from kinematic recordings from body-worn wireless sensors.
Gait Velocity [During the intervention]
Marker of bradykinesia, derived from kinematic recordings from body-worn wireless sensors.
Step Cadence [During the intervention]
Marker of bradykinesia, derived from kinematic recordings from body-worn wireless sensors.
LFP and EEG power spectrum correlation with behavior and kinematics [During the intervention]
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.
LFP and EEG connectivity correlation with behavior and kinematics [During the intervention]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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