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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Disease Progression; Parkinson Disease; Gait Disorders, Neurologic; Deep Brain Stimulation; Accidental Fall; Subthalamic Nucleus
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: James Liao
• Investigators: Principal Investigator: James Liao, MD PhD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Actual): November 15, 2024
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 19, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Freezing of Gait; DBS; Frequency; High; Variable; Postural Instability; Gait Impairment; Low; Alternating
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Disease Attributes; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Disease Progression; Parkinson Disease; Gait Disorders, Neurologic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Dopamine; Dopamine Agonists
• Other Study ID Numbers: 21-739

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At time of publication, a point of contact individual on the study team will be identified. Third parties will be able to request access to de-identified data used to support the publication findings by application to the Cleveland Clinic IRB. A data use agreement will be put in place between the CCF Cleveland Clinic and this third party for approved use of the data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes