Parkinson Disease
Conditions
Keywords
balance disorders, motor functions
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)
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.
Interventions
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.
Sponsors
Michael J. Fox Foundation for Parkinson's Research
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Blood Flow (CBF) Perfusion | 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 |
| Cerebrovascular Reactivity | baseline | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Functional Connectivity | baseline and end of treatment (week 12) | Changes to the within-network connectivity of the DMN (Default Mode Network) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Durability of Change of Functional Connectivity | 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 |
| Change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 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 |
| Change in the Timed Up and Go Test | 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). |
| Change in the Montreal Cognitive Assessment | 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. |
| Change in the Non-Motor Symptom Scale | 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. |
| Change in Cerebral Haemodynamics | 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. |
| Change in Arterial Stiffness | 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. |
| Change in the Parkinson's Anxiety Scale | 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. |
| Change in the Epworth Sleepiness Scale | 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'. |
| Change in the Functional Assessment of Chronic Illness Therapy - Fatigue | 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 |
| Change in the Geriatric Depression Scale | 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. |
| Durability of Change of Cerebral Blood Flow (CBF) Perfusion | 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. |
| Durability of Change of Cerebrovascular Reactivity | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 5 |
| 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. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Treatment 1 | Treatment 2 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 3 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 1 Participants |
| Age, Continuous | 70.6 years STANDARD_DEVIATION 6.97 | 72.2 years STANDARD_DEVIATION 9.2 | 68.5 years STANDARD_DEVIATION 2.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 5 Participants | 4 Participants |
| Region of Enrollment United States | 9 participants | 5 participants | 4 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 2 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
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
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Cerebral Blood Flow (CBF) Perfusion | 35.5 ml/100g/min | Standard Deviation 4.76 |
| Treatment 2 | Cerebral Blood Flow (CBF) Perfusion | 35.2 ml/100g/min | Standard Deviation 5.94 |
Primary
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
Time frame: end of treatment (week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Cerebral Blood Flow (CBF) Perfusion | 33.6 ml/100g/min | Standard Deviation 3.77 |
| Treatment 2 | Cerebral Blood Flow (CBF) Perfusion | 33.3 ml/100g/min | Standard Deviation 10.38 |
Primary
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
Time frame: baseline
Population: Only 3 total participants had usable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Cerebrovascular Reactivity | 1.01 % change CBF/change in CO2 (mmHg) | — |
| Treatment 2 | Cerebrovascular Reactivity | -1.39 % change CBF/change in CO2 (mmHg) | Standard Deviation 1.57 |
Primary
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
Time frame: end of treatment (week 12)
Population: Only 3 total participants had usable data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Cerebrovascular Reactivity | -1.94 % change CBF/change in CO2 (mmHg) | — |
| Treatment 2 | Cerebrovascular Reactivity | -0.7 % change CBF/change in CO2 (mmHg) | Standard Deviation 0.96 |
Secondary
Percent Change in Functional Connectivity
Changes to the within-network connectivity of the DMN (Default Mode Network)
Time frame: baseline and end of treatment (week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Percent Change in Functional Connectivity | 1.1 Percent Change in Default Mode Network | Standard Deviation 21.8 |
| Treatment 2 | Percent Change in Functional Connectivity | 7.5 Percent Change in Default Mode Network | Standard Deviation 19.2 |
Other Pre-specified
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.
Time frame: baseline and end of treatment (week 12)
Other Pre-specified
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.
Time frame: baseline and end of treatment (week 12)
Other Pre-specified
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'.
Time frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Other Pre-specified
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
Time frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Other Pre-specified
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.
Time frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Other Pre-specified
Change in the Montreal Cognitive Assessment
Cognitive screening test - range from zero to 30, with a score of 26 and higher generally considered normal.
Time frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Other Pre-specified
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
Time frame: baseline, end of treatment (week 12), and the post-treatment follow-up (week 17)
Other Pre-specified
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.
Time frame: Change between the baseline and end of treatment (week 12) measure.
Other Pre-specified
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.
Time frame: Change between the baseline and the post-treatment follow-up (week 17) measure.
Other Pre-specified
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.
Time frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Other Pre-specified
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).
Time frame: baseline, end of treatment (week 12) and the post-treatment follow-up (week 17)
Other Pre-specified
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.
Time frame: baseline and the post-treatment follow-up (week 17)
Other Pre-specified
Durability of Change of Cerebrovascular Reactivity
AAT measured using pCASL MRI after a hypercapnic challenge will be used to monitor changes in cerebrovascular reactivity
Time frame: baseline and the post-treatment follow-up (week 17)
Other Pre-specified
Durability of Change of Functional Connectivity
Resting-state magnetic resonance imaging (rs-MRI) will be used to monitor changes in functional connectivity
Time frame: baseline and the post-treatment follow-up (week 17)