Parkinson's DiseasePhase 1/2NCT04768647
Vestibulopathy as a Cause of Imbalance in Parkinson
A Phase 1/2 study testing TNM in people with Parkinson's Disease, run by VA Office of Research and Development at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- TNM
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 May 2021to 30 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105-2303
University of Michigan
Ann Arbor, Michigan, 48105
About this study
Official title: 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.
Read the 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
- Being tested
- TNM
- Keywords
- dopamine, imbalance, vestibular
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNMDevice
Also called Thermoneuromodulation
TNM is a small portable head set that can be used by the participants at home to stimulate the vestibular system
| Study group | Role | What they receive |
|---|---|---|
| Main cohort | No intervention | Main cohort of all patients |
| Subgroup of patients with imbalance | Sham comparator | Subgroup of patients with imbalance Receives: Device: TNM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vestibular function
Assessment of vestibular functions using standard vestibular testing
Measured: through study completion, an average of 4 weeks
Imbalance score
Clinical imbalance motor score
Measured: through study completion, an average of 1 year
Secondary outcomes (1)
DAT brain PET
Dopamine transporter PET
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2021
- Study start28 May 2021
- Primary completion30 Oct 2025
- Study completion30 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is an observational study where a subset of eligible and interested participants can participate in a biomechanistic pilot device study.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- US Department of Veterans Affairs
- Responsible party
- Sponsor
- Investigators
- Nicolaas I Bohnen, MD PhD, Principal investigator, VA Ann Arbor Healthcare System, Ann Arbor, MI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04768647
- Sponsor's protocol ID
- N3397-R
- Other IDs
- 1I01RX003397
- Status last verified
- Apr 2026
- First submitted
- 19 Feb 2021
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vestibulopathy, Imbalance and Gait Disturbances in Parkinson Disease
- ClinicalTrials.gov ID
- NCT04768647
- Acronym / sponsor ID
- N3397-R
- Conditions
- Parkinson's Disease
- Keywords
- dopamine, imbalance, vestibular
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- US Department of Veterans Affairs
- Study start
- 28 May 2021 (actual)
- Primary completion
- 30 Oct 2025 (actual)
- Study completion
- 30 Oct 2025 (actual)
- First posted
- 24 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is an observational study where a subset of eligible and interested participants can participate in a biomechanistic pilot device study.
| Arm | Type | Receives |
|---|---|---|
| Main cohort | No intervention | –Main cohort of all patients |
| Subgroup of patients with imbalance | Sham comparator | Device: TNMSubgroup of patients with imbalance |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNMAlso: ThermoneuromodulationTNM is a small portable head set that can be used by the participants at home to stimulate the vestibular system | Device | Subgroup of patients with imbalance |
Primary outcome
Vestibular function
Time frame: through study completion, an average of 4 weeks
Assessment of vestibular functions using standard vestibular testing
Imbalance score
Time frame: through study completion, an average of 1 year
Clinical imbalance motor score
1 secondary outcome
DAT brain PET
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolaas I Bohnen, MD PhD principal investigator
VA Ann Arbor Healthcare System, Ann Arbor, MI
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TNM in people with Parkinson's Disease, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vestibular function (time frame: through study completion, an average of 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.