Clinical trial NCT04493697: Using Neuromodulation to Improve Parkinson's Disease
Official title: Using Time Varying Non-Invasive Neuromodulation to Improve Neurovascular Status in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Motor/Non-Motor Symptoms
Neurovascular Symptoms
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2020-07-30
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief 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. 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).

Eligibility criteria: Inclusion Criteria:

* 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
* 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)

Exclusion Criteria:

* 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)
* 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

Primary outcomes:
measure: Neuroimaging
timeFrame: Baseline
measure: Neuroimaging
timeFrame: Week 12
measure: Neuroimaging
timeFrame: Week 17
measure: Transcranial Doppler Sonography
timeFrame: Baseline
measure: Transcranial Doppler Sonography
timeFrame: Week 12
Secondary outcomes:
measure: MDS-Unified Parkinson's Disease Rating Scale
timeFrame: Baseline, Week 12, Week 17
measure: Timed Up and Go Test
timeFrame: Baseline, Week 12, Week 17
measure: Montreal Cognitive Assessment
timeFrame: Baseline, Week 12, Week 17
measure: Non-Motor Symptom Scale
timeFrame: Baseline, Week 12, Week 17
measure: Geriatric Depression Scale
timeFrame: Baseline, Week 12, Week 17
measure: Parkinson's Anxiety Scale
timeFrame: Baseline, Week 12, Week 17
measure: Epworth Sleepiness Scale
timeFrame: Baseline, Week 12, Week 17
measure: Functional Assessment of Chronic Illness Therapy - Fatigue -
timeFrame: Baseline, Week 12, Week 17
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest Health Sciences
name: Christopher T Whitlow, MD
role: PRINCIPAL_INVESTIGATOR
References: