STEM-Parkinson's Disease

Study Overview
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Brief Summary
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This is a double-blinded, controlled, randomized clinical trial (RCT) to establish the safety and efficacy of a non-invasive neuromodulation device for treating symptoms associated with Parkinson's disease.

Detailed Description
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Up to 218 participants will enter the double-blinded, controlled, randomized clinical trial (RCT) and will self-administer treatments twice daily in the home setting over a period of 12 weeks following a 4 week baseline period. The RCT will have 6 study visits: 3 visits at the study center and 3 visits completed in the participant's home by video call.

Official Title
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Non-Invasive Brainstem Modulation for the Treatment of Non-Motor Symptoms in Parkinson's Disease: A Randomized Controlled Trial (RCT)

Conditions
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Parkinson Disease, Parkinson's Disease and Parkinsonism

Intervention / Treatment
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* Device: Non-invasive brainstem stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants (aged 18 - 85 years inclusive) Diagnosed with Parkinson's disease according to the UK Brain Bank Criteria Demonstrates a positive response to oral anti-Parkinsonian medications (i.e. dopamine replacement therapies) and treated with these medications for minimum of one year prior to the screening visit Report limitation to activities of daily living (e.g., writing, walking, bathing, dressing, eating, toileting, etc.) Able and willing to consent to participate in the study. Willing and able to comply with study requirements. Anticipate being able to remain on a stable regimen of medications used for the management of PD motor and non-motor symptoms and not to introduce new medications used to treat symptoms associated with PD during the trial. Have at minimum a moderate burden of non-motor symptoms associated with Parkinson's disease Have a study partner (defined as someone who sees the participant for more than one hour a day, 3 times per week) that is willing to consent and participate in the trial. Have capabilities to use and access smartphones and or tablets for the collection of some study data. Must be willing to answer questions related to sexual interest, arousal, and performance in an interview with study staff. Exclusion Criteria: Participant anticipates being unable to attend all visits and complete all study activities. Women of child-bearing potential who are pregnant or plan to become pregnant during the course of the study trial. Women of child-bearing potential , 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 for the entirety of the trial Have a history or prior diagnosis of dementia or evidence of dementia at study screen. Have experienced a myocardial infarction, angina, or stroke within the past 12 months, or a transient ischemic attack within the past 6 months. Are receiving deep brain stimulation therapy. Are treated with a pump for continuous delivery of dopamine replacement medication. Use apomorphine rescue. Have received MRI guided high intensity focused ultrasound within the past 12 months. Experience frequent falls. Work night shifts Use a hearing aid that is implanted or that cannot be easily removed and replaced. Have a cochlear implant. Have chronic (>3 months) tinnitus. Have previously been diagnosed with traumatic brain injury with ongoing sequalae. Have been diagnosed with a co-morbid neurological disorder that may present with symptoms overlapping with PD (e.g., stroke, brain tumor, epilepsy, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, atypical Parkinsonism or aneurysm) Have unresolved complications from a previous surgical procedure at the baseline visits, such as swelling or persistent pain, that requires medical intervention. Have active ear infections, or other significant ear problems. Have a recent history of frequent ear infections (≥ 1 per year over the past two years) Are currently enrolled or have participated in another interventional clinical trial within the last 30 days. Have had eye surgery within the previous three months or ear surgery within the previous six months. Have planned surgery scheduled to occur during the study that requires sedation and/or would typically be followed with a prescription for pain management.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Investigational Treatment 1<br>Investigational treatment mode (stimulation pattern) 1 | Device: Non-invasive brainstem stimulation<br>* Study participants will self-administer  19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device. The device has been deemed to be a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.<br>|
| Other: Investigational Treatment 2<br>Investigational treatment mode (stimulation pattern) 2 | Device: Non-invasive brainstem stimulation<br>* Study participants will self-administer  19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device. The device has been deemed to be a nonsignificant risk for studies in Parkinson's disease by the United States Food and Drug Administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in The International Parkinson and Movement Disorder Society - Non-Motor Rating Scale (MDS-NMS) Total Score | The MDS-NMS is a 52-item rater-administered scale used to assess a wide range of non-motor symptoms in Parkinson's disease. Scores range between 0-832, with the higher score indicating greater non-motor symptom burden. (day 113 score - average of baseline scores from days 1 and 29) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total score (Sum of Parts I, II and III) | The MDS- UPDRS is a multimodal scale consisting of four parts. Part I assesses non-motor aspects of experiences of daily living and consists of two components (range 0-52). Part II is a 13- item patient-reported assessment of motor aspects of experiences of daily living. Scores range between 0-52. Part III assesses motor signs of Parkinson's disease and is completed by the rater (range of 0-132). Part III consists of 33 scores based on 18 items. In all parts, higher scores indicate more symptoms. The range for the MDS-UPDRS total (sum of parts I, II and III) is 0-236. (baseline - week 12) | 3 months | 
| Change from baseline in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II | The MDS-UPDRS Part II is a 13-item patient-reported assessment of motor aspects of experiences of daily living. Scores range between 0-52, with the higher score indicating greater impairment to activities of daily living. (day 113 score - average of baseline scores from days 1 and 29) | 3 months | 
| Change from baseline in the Clinical Global Impression-Improvement (CGI-I) | The CGI-I is a clinician assessment the extent of clinically meaningful change that has occurred in the patient's illness at day 113 relative to a baseline state (assessed at day 29). Changes in all aspects of Parkinson's disease (e.g., motor symptoms, non-motor symptoms and complications of anti-Parkinsonian medications) are considered. | 3 months | 
| Change from baseline in the MDS-UPDRS Part III | The MDS-UPDRS Part III is a 33-item assessment of motor function evaluated by a trained blinded rater. Scores range between 0-132 with higher scores indicating more sever motor symptoms. (day 113 score - average of baseline scores from days 1 and 29) | 3 months | 
| Change from baseline in the Parkinson's Disease Quality of Life Questionnaire Summary Index (PDQ-39 SI) | The PDQ-39 SI is a 39-item patient-reported quality of life measure that assesses how often people living with PD are affected across 8 dimensions of daily living. Scores range from 0-100, with the higher scores indicating worse perception of quality of life. (day 113 score - average of baseline scores from days 1 and 29) | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized Controlled Trial (RCT), Medical Devices, Non-Motor Symptoms (NMS), Non-Invasive Brain Stimulation