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

Using Time Varying Non-Invasive Neuromodulation 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)

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Non-invasive brainstem stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1; Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes	Device: Non-invasive brainstem stimulation; 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.
Experimental: Treatment 2; Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes	Device: Non-invasive brainstem stimulation; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral Blood Flow (CBF) Perfusion	Cerebral blood flow (CBF) measured using pseudo Continuous Arterial Spin Labeling (pCASL) magnetic resonance imaging (MRI) will be used to monitor changes in global perfusion	baseline
Cerebral Blood Flow (CBF) Perfusion	Cerebral blood flow (CBF) 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)
Cerebrovascular Reactivity	Cerebral blood flow is measured with pCASL MRI at baseline and during hypercapnic challenge. The percent change in CBF is divided by the increase in end-tidal CO2 measured in mmHg, measured with RespirACT system	baseline
Cerebrovascular Reactivity	Cerebral blood flow is measured with pCASL MRI at baseline and during hypercapnic challenge. The percent change in CBF is divided by the increase in end-tidal CO2 measured in mmHg, measured with RespirACT system	end of treatment (week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Functional Connectivity	Changes to the within-network connectivity of the DMN (Default Mode Network)	baseline and end of treatment (week 12)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Used to follow the longitudinal course of symptoms of Parkinson's disease - Each parkinsonian sign or symptom is rated on a 5-point Likert-type scale (ranging from 0 to 4), with higher scores indicating more severe impairment. The maximum total UPDRS score is 199, indicating the worst possible disability from PD	baseline, end of treatment (week 12), and the post-treatment follow-up (week 17)
Change in the Timed Up and Go Test	To determine fall risk and measure the progress of balance, sit to stand and walking (ranging from ≤10 seconds as normal to 30 seconds as high fall risk).	baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Change in the Montreal Cognitive Assessment	Cognitive screening test - range from zero to 30, with a score of 26 and higher generally considered normal.	baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Change in the Non-Motor Symptom Scale	Scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease - 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The Non-Motor Symptom Scale measures the severity and frequency of non-motor symptoms across nine dimensions - the total score significantly increased with disease severity and duration meaning that the number of individual non-motor symptoms reported by our patients increases as the disease progresses. Score range 0 - 360.	Change between the baseline and end of treatment (week 12) measure.
Change in the Non-Motor Symptom Scale	Scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease - 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The Non-Motor Symptom Scale measures the severity and frequency of non-motor symptoms across nine dimensions - the total score significantly increased with disease severity and duration meaning that the number of individual non-motor symptoms reported by our patients increases as the disease progresses. Score range 0 - 360.	Change between the baseline and the post-treatment follow-up (week 17) measure.
Change in the Geriatric Depression Scale	A self-report measure of depression in older adults - Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression.	baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Change in the Parkinson's Anxiety Scale	Anxiety assessment - The PAS is a 12-item observer or patient-rated scale with three subscales, for persistent, episodic anxiety and avoidance behavior - There is a maximum total score of 48. Higher scores indicate great experiences of anxiety.	baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Change in the Epworth Sleepiness Scale	A self-administered questionnaire to assess the daytime sleepiness - The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.	baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Change in the Functional Assessment of Chronic Illness Therapy - Fatigue	A tool to help manage chronic illness - The responses to the 13 items on the FACIT fatigue questionnaire are each measured on a 4-point Likert scale. Thus, the total score ranges from 0 to 52. High scores represent less fatigue	baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Change in Arterial Stiffness	Arterial stiffness will be assessed as carotid-femoral pulse wave velocity (PWV). PWV is calculated by dividing the distance between the carotid and femoral arteries by the pulse transit time.	baseline and end of treatment (week 12)
Change in Cerebral Haemodynamics	Transcranial Doppler sonography (TCD), a non-invasive ultrasound, will be used to monitor changes in cerebral blood flow velocity (cm/s) in response to a hypercapnic challenge.	baseline and end of treatment (week 12)
Durability of Change of 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 and the post-treatment follow-up (week 17)
Durability of Change of Cerebrovascular Reactivity	AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity	baseline and the post-treatment follow-up (week 17)
Durability of Change of Functional Connectivity	Resting-state magnetic resonance imaging (rs-MRI) will be used to monitor changes in functional connectivity	baseline and the post-treatment follow-up (week 17)

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Christopher T Whitlow, MD, PhD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 7, 2024

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: October 16, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: balance disorders; motor functions
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: IRB00067408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes