Trial Outcomes & Findings for Use of a Non-Invasive Brainstem Neuromodulation Device to Improve Neurovascular Status in Parkinson's Disease (NCT NCT04598828)

NCT ID: NCT04598828

Last Updated: 2025-08-14

Results Overview

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

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

15 participants

Primary outcome timeframe

baseline

Results posted on

2025-08-14

Participant Flow

Participant milestones

Participant milestones
Measure
Treatment 1
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Overall Study
STARTED
6
6
Overall Study
COMPLETED
5
4
Overall Study
NOT COMPLETED
1
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment 1
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Overall Study
Physician Decision
1
0
Overall Study
Withdrawal by Subject
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment 1
n=5 Participants
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=4 Participants
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Total
n=9 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Age, Categorical
>=65 years
3 Participants
n=5 Participants
3 Participants
n=7 Participants
6 Participants
n=5 Participants
Age, Continuous
72.2 years
STANDARD_DEVIATION 9.20 • n=5 Participants
68.5 years
STANDARD_DEVIATION 2.52 • n=7 Participants
70.6 years
STANDARD_DEVIATION 6.97 • n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants
n=5 Participants
4 Participants
n=7 Participants
9 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
5 Participants
n=5 Participants
4 Participants
n=7 Participants
9 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
5 participants
n=5 Participants
4 participants
n=7 Participants
9 participants
n=5 Participants

PRIMARY outcome

Timeframe: baseline

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

Outcome measures

Outcome measures
Measure
Treatment 1
n=5 Participants
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=4 Participants
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Cerebral Blood Flow (CBF) Perfusion
35.5 ml/100g/min
Standard Deviation 4.76
35.2 ml/100g/min
Standard Deviation 5.94

PRIMARY outcome

Timeframe: end of treatment (week 12)

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

Outcome measures

Outcome measures
Measure
Treatment 1
n=5 Participants
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=4 Participants
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Cerebral Blood Flow (CBF) Perfusion
33.6 ml/100g/min
Standard Deviation 3.77
33.3 ml/100g/min
Standard Deviation 10.38

PRIMARY outcome

Timeframe: baseline

Population: Only 3 total participants had usable data

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

Outcome measures

Outcome measures
Measure
Treatment 1
n=1 Participants
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=2 Participants
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Cerebrovascular Reactivity
1.01 % change CBF/change in CO2 (mmHg)
Standard Deviation NA
For N=1, there is no SD value.
-1.39 % change CBF/change in CO2 (mmHg)
Standard Deviation 1.57

PRIMARY outcome

Timeframe: end of treatment (week 12)

Population: Only 3 total participants had usable data

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

Outcome measures

Outcome measures
Measure
Treatment 1
n=1 Participants
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=2 Participants
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Cerebrovascular Reactivity
-1.94 % change CBF/change in CO2 (mmHg)
Standard Deviation NA
For N=1, there is no SD value.
-0.7 % change CBF/change in CO2 (mmHg)
Standard Deviation 0.96

SECONDARY outcome

Timeframe: baseline and end of treatment (week 12)

Changes to the within-network connectivity of the DMN (Default Mode Network)

Outcome measures

Outcome measures
Measure
Treatment 1
n=5 Participants
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=4 Participants
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Percent Change in Functional Connectivity
1.1 Percent Change in Default Mode Network
Standard Deviation 21.8
7.5 Percent Change in Default Mode Network
Standard Deviation 19.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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'.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Treatment 1

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Treatment 2

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Treatment 1
n=5 participants at risk
Participants will receive Experimental treatment 1 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
Treatment 2
n=4 participants at risk
Participants will receive Experimental treatment 2 stimulation for a duration of 12 weeks, twice daily for 19 minutes 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.
General disorders
Treatment site discomfort
80.0%
4/5 • Number of events 4 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
0.00%
0/4 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
General disorders
Tinnitus
20.0%
1/5 • Number of events 1 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
0.00%
0/4 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
General disorders
Headache
0.00%
0/5 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
25.0%
1/4 • Number of events 1 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
General disorders
Ear pain
0.00%
0/5 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus
25.0%
1/4 • Number of events 1 • 17 weeks
Treatment site discomfort, Headache, Ear pain, Tinnitus

Additional Information

Project Manager

Atrium Health Wake Forest Baptist

Phone: 336-713-8793

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place