Enhancing Gait Using Alternating-Frequency DBS in Parkinson Disease

Phase 1

Recruiting

• Conditions: Parkinson Disease; Gait Disorders, Neurologic; Disease Progression; Subthalamic Nucleus; Accidental Fall; Deep Brain Stimulation
• Interventions: 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

• Registration Number: NCT05022147
• Lead Sponsor: James Liao

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).

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 Timeline

• Study First Submitted: 2021-08-09
• Study First Submitted QC: 2021-08-19
• Study First Posted: 2021-08-26
• Study Start: 2021-10-04
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-15
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Alternating-Frequency DBS	High-Frequency-Only Stimulation	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	Low-Frequency-Only Stimulation	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	Alternating, 50 sec High-Frequency, 10 sec Low-Frequency Stimulation	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	Alternating, 10 sec High-Frequency, 50 sec Low-Frequency Stimulation	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	Alternating, 50 sec High-Frequency, 50 sec Low-Frequency Stimulation	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	Alternating, 10 sec High-Frequency, 10 sec Low-Frequency Stimulation	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	OFF Dopaminergic Medication	In this single-arm study, all participants will receive all interventions in a crossover fashion.
Alternating-Frequency DBS	ON Dopaminergic Medication	In this single-arm study, all participants will receive all interventions in a crossover fashion.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (1)

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States