Vestibulopathy as a Cause of Imbalance in Parkinson

Vestibulopathy, Imbalance and Gait Disturbances in Parkinson Disease

Balance problems and falls are common in people with Parkinson's disease but respond poorly to dopamine stimulating medications suggesting other causes. The main goal of this study is to assess whether imbalance and gait problems in people with Parkinson's disease may be related to vestibular (inner ear balance center) changes not related to loss of dopamine in the brain.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Device: TNM

Detailed Description

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by resting tremor, slowness of movement, rigidity as well as postural instability and gait difficulties (PIGD) motor features. Nigrostriatal dopaminergic denervation is a key pathological factor in PD. Advancing PD is associated with disabling PIGD motor features, in particular freezing of gait (FoG). This is further complicated by fear of falling resulting in pervasive sedentariness where avoidance of physical activity leads to deconditioning, thereby aggravating a downward functional spiral. The dopaminergic medication-refractory nature of PIGD motor features in advancing PD implicates non-dopaminergic brain pathologies.

The investigators have novel preliminary data showing that non-acute vestibulopathy may be another important factor contributing to PIGD motor features in PD. Unlike sporadic intermittent vestibular disorders with a more acute onset, chronic bilateral vestibular dysfunction of older age. The investigators preliminary data suggest that vestibulopathy may be a critical determinant of imbalance and gait problems in PD (scientific premise). However, these preliminary observations need to be confirmed in a larger study using more dedicated assessment methods (knowledge gap). Closing this gap is important because of the potentially high clinical translational impact if preliminary findings can be verified. The investigators will also explore whether stimulation of the vestibular system may help to improve PIGD in a small exploratory pilot biomechanistic sub-study.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48105-2303
      • VA Ann Arbor Healthcare System, Ann Arbor, MI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Veterans with Parkinson's disease

Description

Inclusion Criteria:

• PD based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Research Criteria (n=64, gross recruitment)
• M/F
• age 45 years or older
• duration of disease > 5 years and/or Hoehn & Yahr stages 1.5-4 able to ambulate independently and no evidence of dementia.

Exclusion Criteria:

• History of Meniere disease or recent onset of acute vestibular dysfunction, such as otolith disorders (BBPV etc).
• Other disorders which may resemble PD, such as progressive supranuclear palsy (PSP), vascular dementia, normal pressure hydrocephalus, multiple system atrophy (MSA), corticobasal ganglionic degeneration, or toxic causes of parkinsonism. Prototypical cases have distinctive clinical profiles, like early and severe dysautonomia (MSA) or appendicular apraxia, which may differentiate them from idiopathic PD and PSP. The use of the UKPDSBRC clinical diagnostic criteria for PD will mitigate the inclusion of subjects with atypical parkinsonism.
• Evidence of a stroke or mass lesion on structural brain imaging (MRI).
• Participants in whom MRI is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.
• Severe claustrophobia precluding MR or PET imaging.
• Subjects limited by participation in research procedures involving ionizing radiation.
• Pregnancy (test within 48 hours of each PET session) or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Main cohort; Main cohort of all patients
Sham Comparator: Subgroup of patients with imbalance	Device: TNM; TNM is a small portable head set that can be used by the participants at home to stimulate the vestibular system; Other Names: Thermoneuromodulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vestibular function	Assessment of vestibular functions using standard vestibular testing	through study completion, an average of 4 weeks
Imbalance score	Clinical imbalance motor score	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAT brain PET	Dopamine transporter PET	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: US Department of Veterans Affairs
• Investigators: Principal Investigator: Nicolaas I Bohnen, MD PhD, VA Ann Arbor Healthcare System, Ann Arbor, MI

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): October 30, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: vestibular; dopamine; imbalance
• 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: N3397-R; 1I01RX003397 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes