Clinical trial NCT04768647: Vestibulopathy as a Cause of Imbalance in Parkinson
Official title: Vestibulopathy, Imbalance and Gait Disturbances in Parkinson Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Parkinson's Disease
Keywords: dopamine
imbalance
vestibular
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: US Department of Veterans Affairs
First posted: 2021-02-24
Enrollment: 64
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an observational study where a subset of eligible and interested participants can participate in a biomechanistic pilot device study.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Vestibular function
timeFrame: through study completion, an average of 4 weeks
measure: Imbalance score
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: DAT brain PET
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI
name: Nicolaas I Bohnen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: