Pathways Mediating Impaired Postural Control in Parkinson's Disease

The purpose of this project is to use transcranial magnetic stimulation (TMS) to explore the state of excitability of corticocortical and corticofugal (cortex to spinal cord, cortex to brainstem to spinal cord) pathways that project to muscles that control the legs and trunk in people with Parkinson's disease. The outcome variables will be further analyzed to understand their relationship to quantitative measures of postural instability and gait dysfunction. As such, the project can be classified as basic physiologic research. The protocol is not designed to determine if measures of corticocortical or corticofugal excitability can be used as a biomarker to predict disease progression.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Joshua De Kam; Phone Number: 612-626-8052; Email: jadekam@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants with PD will undergo an initial screening for inclusion/exclusion criteria by their clinician based on findings obtained during their routine clinical appointment.

Potential control participants will be screened for inclusion/exclusion criteria during an initial phone call.

Description

Inclusion Criteria:

Participants with Parkinson's disease

• Diagnosis of idiopathic PD or dystonia as determined by a movement disorders neurologist in accordance with the UK Society Brain Bank diagnostic criteria.
• Age 45-80 years.
• Able to ambulate independently without the use of an assistive device (e.g. cane) for 50 meters.

Healthy Older Adults (Control participants)

• Age 45-80 years (this group will be age and sex-matched to the PD group)
• Able to ambulate independently without the use of an assistive device (cane or walker)

Healthy Young Adults

• Age 21-44 years (this group will be age and sex-matched to the PD group)
• Able to ambulate independently without the use of an assistive device (cane or walker)

Exclusion Criteria:

• Subjects who describe a history of a frequent vasovagal syncope (fainting) in response to blood, emotional stress, or sensory triggers.
• Subjects who are on anti-coagulant medications.
• Any musculoskeletal disorder that affects the ability to stand.
• History of seizures, epilepsy, stroke, multiple sclerosis, or traumatic brain injury.
• Intracranial metallic or magnetic devices.
• Pacemaker or any implanted device.
• History of surgery on blood vessels, brain or heart.
• Unexplained, recurring headaches or concussion within the last six months.
• Moderate to severe hearing impairment.
• Subjects who are pregnant.
• Dementia diagnosis
• Other significant neurological disorders that may affect participation or performance in the study
• Implanted deep brain stimulator or other neurosurgeries to treat PD.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control; 40 healthy older adults and 40 young adults. Potential volunteers for the study will be recruited from a list of volunteers at the University of Minnesota or study information pamphlets distributed people who express an interest in participating (e.g. at research events, support group meetings, or to colleagues of participants tested). Interested individuals will self-identify and contact our research staff for further information.
Experimental; 40 people with Parkinson's disease. Potential volunteers will be recruited from the Movement Disorders Clinic at the University of Minnesota Medical Center. Patients that are referred to this center for standard-of-care evaluations will be seen by a movement disorders neurologist. Patients will be evaluated as per standard of care, regardless of whether they are interested in participating in research protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
average gate speed	Participants will walk on an overground pressure walkway (GAITRite, Franklin, NJ) that provides spatiotemporal measures of walking. In addition, they will wear a set of wearable sensors (APDM Inc., Opals) attached to the feet, wrists and trunk (lumbar and sternum) to capture whole-body motion.	baseline
stride length	Participants will walk on an overground pressure walkway (GAITRite, Franklin, NJ) that provides spatiotemporal measures of walking. In addition, they will wear a set of wearable sensors (APDM Inc., Opals) attached to the feet, wrists and trunk (lumbar and sternum) to capture whole-body motion.	baseline
cadence	Participants will walk on an overground pressure walkway (GAITRite, Franklin, NJ) that provides spatiotemporal measures of walking. In addition, they will wear a set of wearable sensors (APDM Inc., Opals) attached to the feet, wrists and trunk (lumbar and sternum) to capture whole-body motion.	baseline
turn speed	Participants will walk on an overground pressure walkway (GAITRite, Franklin, NJ) that provides spatiotemporal measures of walking. In addition, they will wear a set of wearable sensors (APDM Inc., Opals) attached to the feet, wrists and trunk (lumbar and sternum) to capture whole-body motion.	baseline
ankle rigidity	Quantitative measures of rigidity will be obtained using a custom-built robotic manipulandum. The manipulandum moves the ankle through a sinusoidal or triangular range of motion (25 deg of plantar flexion to 5 degrees of dorsiflexion; modified as needed for participant's range of motion) while measuring the resistive torque generated by ankle impedance.	25mins
Root mean square of the excursion of the center of pressure	Participants will stand on a set of force platforms that measures the forces and pressures beneath the feet. Primary outcome	5mins
single pulse TMS	A measure of the excitability of corticospinal pathways. Primary outcome variables: Peak-to-peak amplitude of the motor evoked potential (MEP) responses to TMS in lower limb and trunk muscles.	1.5hrs
Paired-Pulse TMS (Intracortical excitability):	A measure of the excitability of intracortical (motor cortex-motor cortex) inhibitory (short-intracortical inhibition, SICI) and excitatory (short-intracortical inhibition, ICF) networks. Primary outcome variables: Peak-to-peak amplitude of the motor evoked potential (MEP) responses to TMS in lower limb and trunk muscles.	1hr

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Colum MacKinnon, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): June 10, 2027
• Study Completion (Estimated): June 10, 2027

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: NEUR-2023-31981

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No