Vestibulopathy as a Cause of Imbalance in Parkinson

NCT ID: NCT04768647

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-28
• Study Completion Date: 2025-10-30

Brief Summary

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.

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Main cohort

Main cohort of all patients

Group Type: NO_INTERVENTION

No interventions assigned to this group

Subgroup of patients with imbalance

Subgroup of patients with imbalance

Group Type: SHAM_COMPARATOR

TNM

Intervention Type: DEVICE

TNM is a small portable head set that can be used by the participants at home to stimulate the vestibular system

Interventions

TNM

TNM is a small portable head set that can be used by the participants at home to stimulate the vestibular system

Intervention Type: DEVICE

Other Intervention Names

Thermoneuromodulation

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicolaas I Bohnen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

VA Ann Arbor Healthcare System, Ann Arbor, MI

Locations

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

1I01RX003397

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N3397-R

Identifier Type: -

Identifier Source: org_study_id