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

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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Using Time Varying Non-Invasive Neuromodulation to Improve Neurovascular Status in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Non-invasive brainstem stimulation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment 1<br>Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes | Device: Non-invasive brainstem stimulation<br>* Study participants will self-administer  19-minute treatments twice daily in the home setting using a non-invasive brainstem modulation device. The device has been deemed as a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.<br>|
| Experimental: Treatment 2<br>Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes | Device: Non-invasive brainstem stimulation<br>* Study participants will self-administer  19-minute treatments twice daily in the home setting using a non-invasive brainstem modulation device. The device has been deemed as a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cerebral blood flow (CBF) perfusion | Arterial arrival time (AAT) measured using pseudo Continuous Arterial Spin Labeling (pCASL) magnetic resonance imaging (MRI) will be used to monitor changes in global perfusion. | baseline | 
| Change in cerebral blood flow (CBF) perfusion | Arterial arrival time (AAT) measured using pseudo Continuous Arterial Spin Labeling (pCASL) magnetic resonance imaging (MRI) will be used to monitor changes in global perfusion. | end of treatment (week 12) | 
| Change in cerebrovascular Reactivity | AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity | baseline | 
| Change in cerebrovascular Reactivity | AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity | end of treatment (week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functional connectivity | Resting-state magnetic resonance imaging (rs-MRI) will be used to monitor changes in functional connectivity | baseline and end of treatment (week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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balance disorders, motor functions