Parkinson DiseaseNCT04493697
Using Neuromodulation to Improve Parkinson's Disease
A study testing Experimental 1 and Experimental 2 in people with Parkinson Disease, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
This study is a single-site, double-blinded, placebo-controlled, randomized clinical trial designed to elucidate mechanism(s) of action for symptomatic benefits observed in Parkinson's disease (PD) patients treating twice daily time-varying caloric vestibular stimulation treatment using a solid-state device. Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Experimental 1 and Experimental 2
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2020to Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be 21-85 years old.
- Diagnosed with Parkinson's Disease (meeting UK PD Society Brain Bank criteria)
- Responsive to oral DRT (dopamine replacement therapy) for a minimum of 3 years and on a stable dose of therapy
- Must be able to voluntarily give written informed consent
- Must have ability to reliably use the investigational device
- Must be able to understand and complete all assessments (provided in English only) within a given on-state period
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- Must be willing and able to undertake a ~1 hour imaging session in a MRI magnet with a head coil in place during 3 separate clinic visits.
- Must have a home partner and/or regular caregiver
- Must have capability to complete assessments using telemedicine platforms.
- Must demonstrate moderate burden of motor symptoms and non-motor symptoms in PD ( MDS-UPDRS part II >12 and MDS-UPDRS part I scores >10)
Who cannot join
- Pregnant women.
- Have experienced a heart attack, angina or stroke within the past 12 months,
- Use of medications that regulate heart rate
- Have a history or prior diagnosis of dementia or adjusted score ≤ 20 on the Montreal Cognitive Exam at the baseline visit.
- Those receiving deep brain stimulation
- Treated with a pump for continuous delivery of DRT (Dopamine replacement therapy)
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- Use of Apomorphine rescue
- Works night shifts
- Have a major concomitant illness or illnesses including cancer or disease of the cardiovascular, respiratory and/or renal systems
- Has history or evidence of unstable mood disorder, or responds affirmatively to question #9 on the BDI-II (any score > 0 on suicidal thoughts or wishes). Participants that respond affirmatively to this question should receive a referral for mental health counseling according to the mandates of the IRB or ethics review committee.
- Those with hearing aids or cochlear implants, chronic tinnitus, temporomandibular joint disease
- Those who have persistent negative sequela of a traumatic brain injury
- Those who have been diagnosed with another neurological illness with the exceptions of restless leg syndrome and REM behavioral sleep disorder
- Those with a recent history of substance abuse and/or dependence (alcohol or other drugs)
- Those who have a diagnosed vestibular dysfunction and/or balance dysfunction
- Those who have had eye surgery within the previous three months or ear surgery within the previous six months
- Those who have inner ear pathology, such as active and/or frequent ear infections or reported damage to the tympanic membrane or have labyrinthitis
- Those who have contraindications for MRI imaging, such as metal implants or a pacemaker that would preclude the MRI scan
- Those who have participated in another clinical trial within the last 30 days or are currently enrolled in another clinical trial
- Those who are taking antiemetics chronically (more than 2 times per week, consistently) due to known interference with the vestibular response to caloric stimulation
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Using Time Varying Non-Invasive Neuromodulation to Improve Neurovascular Status in Parkinson's Disease
This study is a single-site, double-blinded, placebo-controlled, randomized clinical trial designed to elucidate mechanism(s) of action for symptomatic benefits observed in Parkinson's disease (PD) patients treating twice daily time-varying caloric vestibular stimulation treatment using a solid-state 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 will be compared to changes in validated standardized clinical measures of motor and non-motor symptoms in PD. The durability of effects will be evaluated at a post-treatment assessment conducted five weeks after treatment cessation.
Read the detailed description
A double-blinded, placebo-controlled randomized trial will explore the effects of time-varying caloric vestibular stimulation (tvCVS) treatments on changes in biomarkers of neurovascular status (i.e. cerebral blood flow perfusion and cerebrovascular reactivity) as well as their relationship to clinical endpoints. Participants will be randomly allocated in a 1:1 ratio using block randomization by the clinical site. Participants will be trained in the clinic to self-administer device treatment and then will continue to self-administer the ~19-minute treatments twice daily for 12 weeks in the home. Individual stimulation sessions will be spaced a minimum of 1 hour apart. Outcome measures will be administered at the baseline, the end of the 12-week treatment period and at 5 weeks post-treatment. Study participants will continue to take their approved Parkinson's disease (PD) medications throughout the study and will maintain patterns of usage throughout.
Previous evidence for efficacy demonstrated therapeutic gains as an adjuvant for standard of care treatment. Consistent with these observations, all outcome measures will be evaluated when study participants are in the on-medication state and at the same time relative to the last dose of anti-Parkinsonian medication across all assessments. Clinical measures will be captured at the baseline, at the end of treatment period, and again five weeks after cessation of treatment. Most of the planned clinical measures including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I, II, and IV, the Non-Motor Symptom Scale for PD (NMSS), the Montreal Cognitive Assessment (MoCA), the Parkinson's Anxiety Scale, the Geriatric Depression Scale, the Epworth Sleepiness Scale, and the Functional Assessment of Chronic Illness Therapy- Fatigue are suitable for virtual collection. Case report forms (CRFs) for the patient reported outcomes will be provided to study participants via standard mail. At the end of each virtual visit, participants will be asked to complete these forms and bring them to the clinic the next day when they come for their in-clinic visit. In the case where an in-clinic visit may not be possible, participants will be asked to show completed forms to the coordinator via the telemedicine platform to confirm completeness, and forms will be collected at the next in-person visit or can be mailed in by the participant.
The full MDS- UPDRS part III and the Timed Up and Go will be administered in the clinic. However, a modified MDS-UPDRS part III (excluding items related to rigidity or postural instability) will also be administered through the telemedicine platform. This measure will serve as backup for cases where participants may be unable to come into the clinic for regularly scheduled assessment (e.g. due to COVID-19 containment measures).
- Conditions
- Parkinson Disease
- Being tested
- Experimental 1, Experimental 2
- Keywords
- Parkinson Disease, Motor/Non-Motor Symptoms, Neurovascular Symptoms
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental 1Device
A ThermoNeuroModulation device will be worn by the participant that delivers warm waveforms in one ear (42 °C) and cool waveforms (17 °C) in the other ear.
Experimental 2Device
A ThermoNeuroModulation device will be worn by the participant that will neither warm nor cool.
| Study group | Role | What they receive |
|---|---|---|
| Experimental 1 | Active comparator | A ThermoNeuroModulation device will be worn by the participant that delivers warm waveforms in one ear (42 °C) and cool waveforms (17 °C) in the other ear. Receives: Device: Experimental 1 |
| Experimental 2 | Placebo comparator | A ThermoNeuroModulation device will be worn by the participant that will neither warm nor cool. Receives: Device: Experimental 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuroimaging
Brain data will be acquired with Siemens MAGNETOM Skyra 3T MRI - range measured by statistically significant change in cerebral blood flow (CBF) measured in units of mL/100g/min
Measured: Baseline
Neuroimaging
Brain data will be acquired with Siemens MAGNETOM Skyra 3T MRI - range measured by statistically significant change in cerebral blood flow (CBF) measured in units of mL/100g/min
Measured: Week 12
Neuroimaging
Brain data will be acquired with Siemens MAGNETOM Skyra 3T MRI - range measured by statistically significant change in cerebral blood flow (CBF) measured in units of mL/100g/min
Measured: Week 17
Transcranial Doppler Sonography
Non-invasive ultrasound used to examine blood circulation within the brain - range measured by statistically significant change in mean cerebral blood flow velocity (cm/s)
Measured: Baseline
Transcranial Doppler Sonography
Non-invasive ultrasound used to examine blood circulation within the brain - range measured by statistically significant change in mean cerebral blood flow velocity (cm/s)
Measured: Week 12
Secondary outcomes (8)
MDS-Unified Parkinson's Disease Rating Scale
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
Measured: Baseline, Week 12, Week 17
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).
Measured: Baseline, Week 12, Week 17
Montreal Cognitive Assessment
Cognitive screening test - range from zero to 30, with a score of 26 and higher generally considered normal.
Measured: Baseline, Week 12, Week 17
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 NMSS measures the severity and frequency of non-motor symptoms across nine dimensions - the total NMSQuest 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.
Measured: Baseline, Week 12, Week 17
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.
Measured: Baseline, Week 12, Week 17
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.
Measured: Baseline, Week 12, Week 17
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'.
Measured: Baseline, Week 12, Week 17
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
Measured: Baseline, Week 12, Week 17
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2020
- Study startSep 2020 (estimated)
- Primary completionSep 2021 (estimated)
- Study completionSep 2022 (estimated)
Why it stopped: Device provider has requested withdrawal citing modifications needed for study integrity.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All participants will receive a ThermoNeuroModulation device for in-home use. Participants will be randomized to either the active or placebo treatment arm.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Sponsor
- Investigators
- Christopher T Whitlow, MD, Principal investigator, Wake Forest Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04493697
- Sponsor's protocol ID
- IRB00067408WD
- Status last verified
- Jul 2020
- First submitted
- 23 Jul 2020
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Time Varying Non-Invasive Neuromodulation to Improve Neurovascular Status in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT04493697
- Acronym / sponsor ID
- IRB00067408WD
- Conditions
- Parkinson Disease
- Keywords
- Parkinson Disease, Motor/Non-Motor Symptoms, Neurovascular Symptoms
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Device provider has requested withdrawal citing modifications needed for study integrity.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- Sep 2020 (estimated)
- Primary completion
- Sep 2021 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 30 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a single-site, double-blinded, placebo-controlled, randomized clinical trial designed to elucidate mechanism(s) of action for symptomatic benefits observed in Parkinson's disease (PD) patients treating twice daily time-varying caloric vestibular stimulation treatment using a solid-state 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 will be compared to changes in validated standardized clinical measures of motor and non-motor symptoms in PD. The durability of effects will be evaluated at a post-treatment assessment conducted five weeks after treatment cessation.
Detailed description
A double-blinded, placebo-controlled randomized trial will explore the effects of time-varying caloric vestibular stimulation (tvCVS) treatments on changes in biomarkers of neurovascular status (i.e. cerebral blood flow perfusion and cerebrovascular reactivity) as well as their relationship to clinical endpoints. Participants will be randomly allocated in a 1:1 ratio using block randomization by the clinical site. Participants will be trained in the clinic to self-administer device treatment and then will continue to self-administer the ~19-minute treatments twice daily for 12 weeks in the home. Individual stimulation sessions will be spaced a minimum of 1 hour apart. Outcome measures will be administered at the baseline, the end of the 12-week treatment period and at 5 weeks post-treatment. Study participants will continue to take their approved Parkinson's disease (PD) medications throughout the study and will maintain patterns of usage throughout.
Previous evidence for efficacy demonstrated therapeutic gains as an adjuvant for standard of care treatment. Consistent with these observations, all outcome measures will be evaluated when study participants are in the on-medication state and at the same time relative to the last dose of anti-Parkinsonian medication across all assessments. Clinical measures will be captured at the baseline, at the end of treatment period, and again five weeks after cessation of treatment. Most of the planned clinical measures including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I, II, and IV, the Non-Motor Symptom Scale for PD (NMSS), the Montreal Cognitive Assessment (MoCA), the Parkinson's Anxiety Scale, the Geriatric Depression Scale, the Epworth Sleepiness Scale, and the Functional Assessment of Chronic Illness Therapy- Fatigue are suitable for virtual collection. Case report forms (CRFs) for the patient reported outcomes will be provided to study participants via standard mail. At the end of each virtual visit, participants will be asked to complete these forms and bring them to the clinic the next day when they come for their in-clinic visit. In the case where an in-clinic visit may not be possible, participants will be asked to show completed forms to the coordinator via the telemedicine platform to confirm completeness, and forms will be collected at the next in-person visit or can be mailed in by the participant.
The full MDS- UPDRS part III and the Timed Up and Go will be administered in the clinic. However, a modified MDS-UPDRS part III (excluding items related to rigidity or postural instability) will also be administered through the telemedicine platform. This measure will serve as backup for cases where participants may be unable to come into the clinic for regularly scheduled assessment (e.g. due to COVID-19 containment measures).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- All participants will receive a ThermoNeuroModulation device for in-home use. Participants will be randomized to either the active or placebo treatment arm.
| Arm | Type | Receives |
|---|---|---|
| Experimental 1 | Active comparator | Device: Experimental 1A ThermoNeuroModulation device will be worn by the participant that delivers warm waveforms in one ear (42 °C) and cool waveforms (17 °C) in the other ear. |
| Experimental 2 | Placebo comparator | Device: Experimental 2A ThermoNeuroModulation device will be worn by the participant that will neither warm nor cool. |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Must be 21-85 years old.
- Diagnosed with Parkinson's Disease (meeting UK PD Society Brain Bank criteria)
- Responsive to oral DRT (dopamine replacement therapy) for a minimum of 3 years and on a stable dose of therapy
- Must be able to voluntarily give written informed consent
- Must have ability to reliably use the investigational device
Key exclusion criteria (20 listed)
- Pregnant women.
- Have experienced a heart attack, angina or stroke within the past 12 months,
- Use of medications that regulate heart rate
- Have a history or prior diagnosis of dementia or adjusted score ≤ 20 on the Montreal Cognitive Exam at the baseline visit.
- Those receiving deep brain stimulation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental 1A ThermoNeuroModulation device will be worn by the participant that delivers warm waveforms in one ear (42 °C) and cool waveforms (17 °C) in the other ear. | Device | Experimental 1 |
| Experimental 2A ThermoNeuroModulation device will be worn by the participant that will neither warm nor cool. | Device | Experimental 2 |
Primary outcome
Neuroimaging
Time frame: Baseline
Brain data will be acquired with Siemens MAGNETOM Skyra 3T MRI - range measured by statistically significant change in cerebral blood flow (CBF) measured in units of mL/100g/min
Neuroimaging
Time frame: Week 12
Brain data will be acquired with Siemens MAGNETOM Skyra 3T MRI - range measured by statistically significant change in cerebral blood flow (CBF) measured in units of mL/100g/min
Neuroimaging
Time frame: Week 17
Brain data will be acquired with Siemens MAGNETOM Skyra 3T MRI - range measured by statistically significant change in cerebral blood flow (CBF) measured in units of mL/100g/min
Transcranial Doppler Sonography
Time frame: Baseline
Non-invasive ultrasound used to examine blood circulation within the brain - range measured by statistically significant change in mean cerebral blood flow velocity (cm/s)
Transcranial Doppler Sonography
Time frame: Week 12
Non-invasive ultrasound used to examine blood circulation within the brain - range measured by statistically significant change in mean cerebral blood flow velocity (cm/s)
8 secondary outcomes
MDS-Unified Parkinson's Disease Rating Scale
Time frame: Baseline, Week 12, Week 17
Timed Up and Go Test
Time frame: Baseline, Week 12, Week 17
Montreal Cognitive Assessment
Time frame: Baseline, Week 12, Week 17
Non-Motor Symptom Scale
Time frame: Baseline, Week 12, Week 17
Geriatric Depression Scale
Time frame: Baseline, Week 12, Week 17
Parkinson's Anxiety Scale
Time frame: Baseline, Week 12, Week 17
Epworth Sleepiness Scale
Time frame: Baseline, Week 12, Week 17
Functional Assessment of Chronic Illness Therapy - Fatigue -
Time frame: Baseline, Week 12, Week 17
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher T Whitlow, MD principal investigator
Wake Forest Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Experimental 1 and Experimental 2 in people with Parkinson Disease, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuroimaging (time frame: Baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2020.