Personalized Real-Time DBS and PD Mechanisms

May 12, 2026 updated by: David Escobar

Identifying Circuit Dynamics Underlying Motor Dysfunction in Parkinson's Disease Using Real-Time Neural Control

A prospective cohort of patients scheduled to undergo deep brain stimulation (DBS) implantation surgery for the treatment of Parkinson's disease as per standard of care will be invited to participate in this study. This mechanistic study is aimed at better understanding the role of basal ganglia beta band (11-35 Hz) oscillations and resonance in the manifestation of Parkinson's disease (PD) motor signs using closed-loop electrical neurostimulation, levodopa medication, and computational modeling. The ultimate goal of this study is to inform the development of closed-loop neuromodulation technology that can be programmed and adjusted in real time based on patient-specific neural activity.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

While much research has been dedicated to understanding the pathophysiology of Parkinson's disease (PD), the neural dynamics underlying the manifestation of motor signs remain unclear. Studies over the past two decades have shown a correlation of the amplitude and incidence of beta band oscillations in the subthalamic nucleus (STN) with changes in bradykinesia and rigidity mediated by levodopa or deep brain stimulation (DBS) therapies. Yet, no study has conclusively or deductively demonstrated a causal link. A limitation to establishing causality is the lack of available neuromodulation tools capable of predictably and precisely controlling neural oscillatory activity in the human brain in real time without introducing confounding factors. Establishing these tools and clarifying whether the relationship of beta band oscillations with PD motor signs is causal or epiphenomenon are critical steps to better understand PD pathophysiology and advance personalized DBS technology in PD and other brain conditions. This study aims to address these technology and knowledge gaps by leveraging feedback control engineering and patient-specific computational modeling tools.

In this study, the investigators will employ a neural control approach, referred to as evoked interference closed-loop DBS (eiDBS), to characterize the degree by which controlled suppression or amplification of beta oscillations in the STN influences bradykinesia and rigidity in PD (Specific Aim 1, SA1). The investigators will test the hypothesis that stimulation-induced suppression or amplification of beta oscillations in the STN will result in changes in bradykinesia and rigidity measures. In SA2, the investigators will employ levodopa medication to characterize how changes in bradykinesia and rigidity relate to variations in the amplitude of neural oscillations in the STN and primary motor cortex (MC) evoked by STN stimulation. The investigators will test the hypothesis that levodopa administration will result in a decrease in the amplitude of stimulation-evoked beta oscillations that will correlate with changes in bradykinesia and rigidity. The results from SA2 will help to gain a greater understanding of intrinsic circuit dynamics associated with PD and identify strategies to optimize closed-loop DBS algorithms (e.g., eiDBS) in the face of concurrent levodopa therapy, a step to bring this technology to future clinical trials. Combining electrophysiological data with high-resolution (7T) magnetic resonance (MR) imaging and computational modeling, the investigators will examine which specific neuronal pathways connected with the STN need to be activated to evoke frequency-specific neural responses in the STN and MC (SA3). The data from SA3 will shed light on which sub-circuits are involved in the generation of stimulation-evoked and spontaneous beta oscillations in PD, and inform how to use directional DBS leads to shape electric fields in the STN to selectively modulate the STN via eiDBS or other neurostimulation techniques. The investigators will address the three aims of this study with the participation of PD patients implanted with DBS leads in the STN, whose DBS lead extensions will be externalized and connected to our recording and closed-loop stimulation infrastructure.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Ability to provide informed consent.
  • Clinical diagnosis of idiopathic Parkinson's disease.
  • Determined, as per standard of care, to be a candidate for deep brain stimulation (DBS) surgery targeting the subthalamic nucleus.
  • Ability to tolerate delays in taking daily standard Parkinson's disease medications.

Key Exclusion Criteria:

  • Secondary Parkinsonism, stroke, or progressive central nervous system disease other than Parkinson's disease.
  • Patient has a condition that, in the opinion of the investigators, would significantly increase the risk of interfering with study compliance, safety, or outcome.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: eiDBS suppression
Closed-loop evoked interference DBS that suppresses beta oscillations.
Device: Neurostimulation
Electrical stimulation delivered via deep brain stimulation electrodes based on measurements of brain activity.
No Intervention: Off DBS
Off-stimulation and off-medication
Experimental: eiDBS amplification
Closed-loop evoked interference DBS that amplifies beta oscillations.
Device: Neurostimulation
Electrical stimulation delivered via deep brain stimulation electrodes based on measurements of brain activity.
Experimental: Levodopa medication
On-medication, off-stimulation
Drug: Carbidopa 25/Levodopa 100Mg Tab
Anti-parkinsonian medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of eiDBS suppression vs. off-stimulation on finger tapping speed
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The finger tapping speed will be measured with an inertial measuring unit. The relationship (slope/effect) between this kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models. The LME models will include the stimulation conditions in this study (e.g., eiDBS-suppression) as fixed effects with the off-stimulation condition as a reference/control group, and random intercepts as random effects that account for the heterogeneity between subjects.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS amplification vs. off-stimulation on finger tapping speed
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between the kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS suppression vs. off-stimulation on forearm speed
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The forearm speed will be measured with an inertial measuring unit. The relationship (slope/effect) between this kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS amplification vs. off-stimulation on forearm speed
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between the kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS suppression vs. off-stimulation on UPDRS-III rigidity subscore
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between this UPDRS-III rigidity subscore (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS amplification vs. off-stimulation on UPDRS-III rigidity subscore
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between this UPDRS-III rigidity subscore (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Correlation between levodopa-related changes in finger tapping speed and the amplitude of stimulation-evoked beta oscillations
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The amplitude of beta oscillations evoked by stimulation will be characterized using the wavelet transform. The relationship (slope) between the kinematic measurements (response variable) and the beta oscillations amplitude (predictor variable) will be estimated via the linear mixed-effects models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Correlation between levodopa-related changes in forearm speed and the amplitude of stimulation-evoked beta oscillations
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope) between the kinematic measurements (response variable) and the beta oscillations amplitude (predictor variable) will be estimated via the linear mixed-effects models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Correlation between levodopa-related changes in UPDRS-III rigidity subscore and the amplitude of stimulation-evoked beta oscillations.
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope) between the UPDRS-III subscores (response variable) and the beta oscillations amplitude (predictor variable) will be estimated via the linear mixed-effects models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of eiDBS suppression vs. off-stimulation on finger tapping displacement
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The finger tapping displacement will be derived based on data from an inertial measuring unit via a Kalman filter. The relationship (slope/effect) between this kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS amplification vs. off-stimulation on finger tapping displacement
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between the kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS suppression vs. off-stimulation on forearm displacement
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between the kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS amplification vs. off-stimulation on forearm displacement
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between the kinematic variable (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS suppression vs. off-stimulation on UPDRS-III bradykinesia subscore
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between this UPDRS-III subscore (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Effect of eiDBS amplification vs. off-stimulation on UPDRS-III bradykinesia subscore
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope/effect) between this UPDRS-III subscore (response variable) and the mean amplitude of beta (11-35 Hz) oscillations (predictor physiological variable) will be estimated via linear mixed-effects (LME) models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Correlation between levodopa-related changes in finger tapping displacement and the amplitude of stimulation-evoked beta oscillations
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope) between the kinematic measurements (response variable) and the beta oscillations amplitude (predictor variable) will be estimated via the linear mixed-effects models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Correlation between levodopa-related changes in forearm displacement and the amplitude of stimulation-evoked beta oscillations
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope) between the kinematic measurements (response variable) and the beta oscillations amplitude (predictor variable) will be estimated via the linear mixed-effects models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
Correlation between levodopa-related changes in UPDRS-III bradykinesia subscore and the amplitude of stimulation-evoked beta oscillations
Time Frame: Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.
The relationship (slope) between the UPDRS-III subscores (response variable) and the beta oscillations amplitude (predictor variable) will be estimated via the linear mixed-effects models.
Data will be collected in assessment blocks multiple times throughout enrollment. Assessments will be performed for up to nine days, starting the day after the DBS surgery. Assessments may also be performed in one visit 3-12 months after DBS surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David Escobar

Collaborators

The Cleveland Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 29, 2023

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

August 22, 2023

First Submitted That Met QC Criteria

August 25, 2023

First Posted (Actual)

August 28, 2023

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-358

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in the published articles (text, tables, figures, and appendices), after deidentification, will be shared.

IPD Sharing Time Frame

Data will be shared immediately following publication. There is no end date for this data sharing.

IPD Sharing Access Criteria

Data sharing requests should be directed to escobad2@ccf.org. To gain access, data requestors may need to sign a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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