The Impact of Exercise on Subthalamic Nucleus Neural Activity in Parkinson's Disease

NCT ID: NCT05905302

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-15
• Study Completion Date: 2024-09-20

Brief Summary

Fifteen PwPD who have undergone DBS surgery and utilize the Percept system will complete a FE and VE exercise session on a stationary cycle while Off antiparkinsonian medication. Bilateral neural activity of the STN will be continuously recorded for 130 minutes (pre-, during FE or VE and post-exercise). The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III Motor Exam and upper extremity force-tracking task will be used to determine motor response to exercise.

Detailed Description

Parkinson's disease (PD) is a progressive neurological disease, most prevalent in older adults, estimated to affect over 12 million people world-wide by 2040. While antiparkinsonian medication and deep brain simulation (DBS) are effective in managing disease symptoms, disease modification has remained elusive. Exercise has been proposed as the Universal Prescription for PD capable of slowing disease progression; stationary cycling in particular has been suggested as an ideal exercise modality for people with PD (PwPD).Our seminal tandem cycling study was the first to utilize forced exercise (FE) in human PD patients and demonstrate a 30% improvement in clinical ratings compared to voluntary exercise (VE). Briefly, FE is a mode of high intensity exercise originating in animal models of PD in which voluntary exercise rate is augmented, but not replaced. Thus, PwPD were assisted in pedaling at a higher rate (cadence) on the tandem cycle compared to those on a standard stationary cycle performing voluntary exercise (VE). This work resulted in a paradigm shift in terms of recommending high intensity exercise for PwPD. Currently, we are involved in two multi-site clinical trials aimed at identifying the potential of high intensity exercise to slow PD (2R01NS073717 & 1U01NS113851). Despite the potential of exercise to alter disease progression, its mechanism of action and effects on basal ganglia function are not understood. The loss of dopamine producing neurons associated with PD results in hypersynchrony of basal ganglia motor circuits that underlies PD symptoms. Recent animal studies using FE evaluated neural activity, local field potentials (LFPs), from the primary motor cortex (M1) to estimate the impact of exercise on basal ganglia function. Following FE, neural hypersynchrony in the beta (13-35Hz) frequency band was reduced in M1, which was proposed to underlie improved motor function. M1 activity is impacted by the activity in the subthalamic nucleus (STN), a structure in the basal ganglia, via the direct and indirect pathways. The impact of high intensity exercise, VE or FE, on STN hypersynchrony in humans is unknown. Recording of STN neural activity, until recently, was only possible during DBS surgery or in patients whose electrode was temporarily externalized immediately post-surgery. Neither approach is feasible or safe to systematically evaluate the effects of exercise on basal ganglia function. Recently, the Medtronic Percept DBS platform received FDA approval. The Percept platform records and streams neural activity from the DBS electrode within the STN. This project, for the first time, will record neural activity from the STN during two modes of high intensity exercise, FE and VE, in PwPD to identify the potential mechanism underlying the beneficial effects of exercise on PD. Our underlying hypothesis is that high intensity exercise reduces STN hypersynchrony which facilitates cortico-basal ganglia-thalamocortical circuit functionality thereby improving motor function following exercise.

Conditions

Parkinson Disease; Deep Brain Stimulation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Experimental Arm

Two modes of high intensity exercise

Group Type: EXPERIMENTAL

Forced and Voluntary Exercise

Intervention Type: OTHER

Participants will complete a forced exercise (FE) and voluntary exercise (VE) session. Forced exercise is a mode of high intensity exercise in which voluntary exercise rate is augmented, but not replaced. Voluntary exercise is standard stationary cycling. FE and VE exercise sessions will be Off antiparkinsonian medication. The order in which exercise session is conducted first will be randomized. Bilateral neural activity of the STN will be continuously recorded for 130 minutes (pre, during FE or VE and post-exercise).

Interventions

Forced and Voluntary Exercise

Participants will complete a forced exercise (FE) and voluntary exercise (VE) session. Forced exercise is a mode of high intensity exercise in which voluntary exercise rate is augmented, but not replaced. Voluntary exercise is standard stationary cycling. FE and VE exercise sessions will be Off antiparkinsonian medication. The order in which exercise session is conducted first will be randomized. Bilateral neural activity of the STN will be continuously recorded for 130 minutes (pre, during FE or VE and post-exercise).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Adult with a diagnosis of PD by a movement disorders neurologist

2. Previous placement, at least six months, of bilateral Medtronic Precept DBS as standard of care treatment for their PD.

3. Stable and clinically optimized DBS parameters for three months prior to enrollment.

4. Demonstrate the ability to safely mount and dismount a recumbent exercise cycle with an upright back.

5. Willingness to withhold antiparkinsonian medication and DBS stimulation.

6. Exercise clearance using the American College of Sports Medicine (ACSM) Pre-participation Health Screen: a. If the ACSM screen recommends medical clearance, the subject must obtain medical clearance by their health care provider prior to participation; b. Those who choose not to obtain physician clearance will not be eligible for participation.

Exclusion Criteria

1. Diagnosis of dementia or any neurocognitive impairment that compromises the ability to provide informed consent.

2. A musculoskeletal issue that limits one's ability to cycle

3. Neurological disease other than Parkinson's disease (i.e. multiple sclerosis, stroke) that impacts motor or cognitive function

4. Uncontrolled cardiovascular risk factor such as a current cardiac arrhythmia, uncontrolled hypertension, untreated deep vein thrombosis, etc.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jay Alberts

OTHER

Sponsor Role: lead

Responsible Party

Jay Alberts

Staff

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jay Alberts, PhD

Role: PRINCIPAL_INVESTIGATOR

Staff

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

References

Koop MM, Rosenfeldt AB, Berki V, Bazyk A, Davidson S, Malan NS, Nagel S, Walter BL, Liao JY, Alberts JL. A novel methodological approach to understanding the cortical and subcortical effects of aerobic exercise in Parkinson's disease. Front Hum Neurosci. 2025 Oct 20;19:1657049. doi: 10.3389/fnhum.2025.1657049. eCollection 2025.

Reference Type: DERIVED

PMID: 41189627 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R21NS129147-01

Identifier Type: NIH

Identifier Source: org_study_id

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