Use of a Non-Invasive Brainstem Neuromodulation Device to Improve Neurovascular Status in Parkinson's Disease

This study is a single-site, double-blinded, randomized clinical trial designed to elucidate mechanism(s) of action for symptomatic benefits observed in Parkinson's disease (PD)

Patients treating twice daily using a non-invasive brainstem modulation device. Study participants will self-administer treatments in the home setting over a period of 12 weeks. Changes in cerebral blood flow perfusion, cerebrovascular reactivity and functional connectivity between the pre-treatment baseline and the end of the treatment period will be monitored and compared to changes in validated standardized clinical measures of motor and non-motor symptoms in PD.

Eligibility Criteria:
Inclusion Criteria:

* Must be 21-85 years old
* Diagnosed with Parkinson's Disease
* Within driving distance of Atrium Health Wake Forest Baptist (Winston-Salem, NC)
* Responsive to Parkinson's medication for a minimum of 3 years
* Have ability to reliably use the investigational device
* Understand and complete all assessments (provided in English only)
* Be able to have 3 separate MRI scans (1.5 hours per MRI)
* Have a study partner/regular caregiver that is willing to participate in the trial
* Demonstrate moderate burden of motor symptoms and non-motor symptoms
* Consent to being videotaped during motor examination visit
* Willing to answer questions related to sexual interest, arousal and performance in an interview with study staff

Exclusion Criteria:

* Cannot attend all study visits (4 on-site visits) or complete all study activities
* Heart attack, angina, or stroke within the past year
* Use medications that regulate heart rate
* Have a history or prior diagnosis of dementia
* Receiving deep brain stimulation therapy
* Treated with a pump for continuous delivery of dopamine replacement therapy
* Use of Apomorphine rescue
* Works night shifts
* Have any significant co-morbidity such as stroke, brain tumor, epilepsy, Alzheimer's disease, multiple sclerosis, ALS, atypical Parkinsonism, or aneurysm
* History or evidence of unstable mood disorder or demonstrates evidence of suicidality
* Hearing aids that are implanted or cannot be easily removed and replaced, such as cochlear implants
* Chronic ringing in the ears for more than 3 months
* Diagnosed with traumatic brain injury with ongoing symptoms
* Recent history of substance abuse and/or dependence (alcohol or other drugs)
* Diagnosed balance dysfunction
* Eye surgery within the previous 3 months
* Ear surgery within the previous 6 months
* Active ear infection, perforated tympanic membrane, or inner ear inflammation
* Recent history of frequent ear infections (≥ 1 per year over the past two years)
* Contraindications for MRI scans, such as metal implants or a pacemaker
* Currently enrolled or have participated in another interventional clinical trial within the last 30 days
* Taking medication for vomiting or nausea more than 2 times per week, consistently
* Ongoing symptoms from a COVID-19 infection that includes one or more of the exclusion criteria listed above
* Planned surgery scheduled to occur during the clinical trial that requires sedation and/or would typically be followed with a prescription for pain management
* Women who are pregnant or plan to become pregnant during the the study

Women of child-bearing potential (i.e., are not yet 3 years removed from their first menopausal symptom), who are not abstinent or exclusively in same sex relationships must:

Test negative for pregnancy as indicated by a negative urine pregnancy test

Agree to use an approved contraception method