STEM-Parkinson's Disease

Inclusion Criteria

• Adult participants (aged 18 - 85 years inclusive)
• Diagnosed with Parkinson's disease according to the UK Brain Bank Criteria (allowing for an exclusion in Step 2 for "more than one affected relative").
• Demonstrates a sustained, positive response to dopamine replacement therapies (DRTs) (e.g., levodopa, dopamine agonists or monoamine oxidase inhibitors) defined as either good or excellent responses (50-100%) for at least one year or moderate responses (30-49)% for at least three years prior to screen.
• Participant-reported or clinician-investigator-determined limitation, based on knowledge of medical history, to one or more 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.
• Participants and investigators must expect that the participant will be able to remain on a stable regimen of concomitant therapies used for the management of PD motor and non-motor symptoms and not to introduce new medications used to treat motor or non-motor symptoms associated with PD during the study.
• Have at minimum a moderate burden of non-motor symptoms associated with Parkinson's disease (i.e., MDS-UPDRS part Ia and part Ib summed total score ≥ 9) at study screen to avoid floor effects for the primary endpoint (MDS-NMS).
• The principal investigator or designee must have confidence in the participant's ability to reliably use the TNM™ device, understand the assessments (provided in English only) and to complete the assessment battery within a given on-state period.
• 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 and/or tablets or computers for access to telemedicine platforms.
• 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 or adjusted score ≤ 20 on the Montreal Cognitive Assessment (MoCA) at the screening visit
• 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.
• Have received MRI guided high intensity focused ultrasound within the past 12 months.
• Experience frequent falls. (defined as 2 or more falls in the past month related to Parkinson's disease). Parkinson's falls are defined as falls associated with bradykinesia, freezing, turning, change in posture and postural dizziness and do not include accidental falls.
• Work night shifts
• Use a hearing aid that is implanted or that cannot be easily removed and replaced.
• Has any significant co-morbidity or illness which in the opinion of the investigator would prevent safe participation in the study, compliance with protocol requirements or which presents with symptoms that are also common in PD.
• Demonstrate suicidality at screening (scores ≥ 4 on the C-SSRS Baseline in section "Suicidal Ideation" (In the past Month)). Participants that respond affirmatively to question 4 or 5 (In the past Month) should receive a referral for mental health counseling