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

• ClinicalTrials.gov Identifier: NCT04598828
• Recruitment Status: Recruiting
• First Posted: October 22, 2020
• Last Update Posted: March 4, 2022
• Sponsor: Wake Forest University Health Sciences
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Device: Non-invasive brainstem stimulation	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Using Time Varying Non-Invasive Neuromodulation to Improve Neurovascular Status in Parkinson's Disease
• Actual Study Start Date: July 6, 2021
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in cerebral blood flow (CBF) perfusion [ Time Frame: baseline ]
   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.
2. Change in cerebral blood flow (CBF) perfusion [ Time Frame: end of treatment (week 12) ]
   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.
3. Change in cerebrovascular Reactivity [ Time Frame: baseline ]
   AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity
4. Change in cerebrovascular Reactivity [ Time Frame: end of treatment (week 12) ]
   AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity

Secondary Outcome Measures :

1. Change in functional connectivity [ Time Frame: baseline and end of treatment (week 12) ]
   Resting-state magnetic resonance imaging (rs-MRI) will be used to monitor changes in functional connectivity

Other Outcome Measures:

1. Change in cerebral haemodynamics [ Time Frame: baseline and end of treatment (week 12) ]
   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.
2. Durability of change of cerebral blood flow (CBF) perfusion [ Time Frame: baseline and the post-treatment follow-up (week 17) ]
   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.
3. Durability of change of cerebrovascular Reactivity [ Time Frame: baseline and the post-treatment follow-up (week 17) ]
   AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity
4. Durability of change of functional connectivity [ Time Frame: baseline and the post-treatment follow-up (week 17) ]
   Resting-state magnetic resonance imaging (rs-MRI) will be used to monitor changes in functional connectivity
5. Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [ Time Frame: baseline, end of treatment (week 12), and the post-treatment follow-up (week 17) ]
   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
6. Change in the Timed Up and Go Test [ Time Frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17) ]
   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).
7. Change in the Montreal Cognitive Assessment [ Time Frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17) ]
   Cognitive screening test - range from zero to 30, with a score of 26 and higher generally considered normal.
8. Change in the Non-Motor Symptom Scale [ Time Frame: Change between the baseline and end of treatment (week 12) measure. ]
   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.
9. Change in the Non-Motor Symptom Scale [ Time Frame: Change between the baseline and the post-treatment follow-up (week 17) measure. ]
   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.
10. Change in the Geriatric Depression Scale [ Time Frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17) ]
    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.
11. Change in the Parkinson's Anxiety Scale [ Time Frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17) ]
    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.
12. Change in the Epworth Sleepiness Scale [ Time Frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17) ]
    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'.
13. Change in the Functional Assessment of Chronic Illness Therapy - Fatigue [ Time Frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17) ]
    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
14. Change in Arterial Stiffness [ Time Frame: baseline and end of treatment (week 12) ]
    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.

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Christopher T Whitlow, MD, PhD; 336-713-8793; cwhitlow@wakehealth.edu

Contact: Richarlette C Hightower, BA; 336-713-8793; rhightow@wakehealth.edu

Locations

United States, North Carolina

Wake Forest Health Sciences; Recruiting

Winston-Salem, North Carolina, United States, 27157

Contact: Richarlette C Hightower rhightow@wakehealth.edu

Contact: Christopher T Whitlow, MD, PhD, MHA

Principal Investigator: Christoper T Whitlow, MD, PhD, MHA

Sponsors and Collaborators

Wake Forest University Health Sciences

Investigators

• Principal Investigator: Christopher T Whitlow, MD, PhD; Wake Forest University Health Sciences

More Information

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT04598828
• Other Study ID Numbers: IRB00067408
• First Posted: October 22, 2020
• Last Update Posted: March 4, 2022
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual participant data (IPD) will not be available to other researchers.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Wake Forest University Health Sciences:

balance disorders; motor functions

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases