Vestibulopathy as a Cause of Imbalance in Parkinson

Parkinson's Disease Clinical Trial

Official title:

Vestibulopathy, Imbalance and Gait Disturbances in Parkinson Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04768647
• Other study ID #: N3397-R
• Secondary ID: 1I01RX003397
• Status: Recruiting
• Start date: May 28, 2021
• Est. completion date: May 31, 2025

Study information

• Verified date: April 2024
• Source: VA Office of Research and Development
• Contact: Nicolaas I Bohnen, MD PhD
• Phone: (734) 769-7100
• Email: nicolaas.bohnen[@]va.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	US Department of Veterans Affairs

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vestibular function	Assessment of vestibular functions using standard vestibular testing	through study completion, an average of 4 weeks
Primary	Imbalance score	Clinical imbalance motor score	through study completion, an average of 1 year
Secondary	DAT brain PET	Dopamine transporter PET	through study completion, an average of 1 year