STEM-Parkinson's Disease

Not Applicable

Completed

Conditions: Parkinson Disease
Parkinson's Disease and Parkinsonism

Interventions: Device: Non-invasive brainstem stimulation

Registration Number: NCT04797611

Lead Sponsor: Scion NeuroStim

Brief Summary: This is a double-blinded, controlled, and 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: The double-blinded, controlled, randomized clinical trial (RCT) will be conducted at 15 centers, at minimum, in the United States and the United Kingdom with the majority of centers in the United States. Up to 184 participants will enter and will self-administer treatments twice daily in their home setting over a period of 12 weeks following a 4 week baseline period. Each participant will complete 6 study visits: 3 visits at the study center and 3 visits completed in the participant's home by video call.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 218

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:
1. Test negative for pregnancy as indicated by a negative urine pregnancy test
2. 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 according to local site regulations and standards
Use a hearing aid that is implanted or that cannot be easily removed and replaced
Have a cochlear implant or myringotomy tubes
Have chronic that has been ongoing for at least 3 months and causes significant impairment of communication and/or impairment of activities of daily living.
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 been previously diagnosed with either clinically meaningful central vestibular dysfunction (lifetime) or have experienced clinically meaningful peripheral vestibular dysfunction within the last 12 months. For this purpose, clinically meaningful is defined as vestibular dysfunction which causes at least a minimal impairment in the individual activities of daily living (e.g., dressing, bathing, preparing food, conducting household chores, work or recreational activities).
In the Investigator's opinion, currently abuse alcohol, abuse drugs (including legal, illegal or prescribed drugs) or have a history of alcohol or drug dependency within the past 5 years or use any drugs excluded as noted in the Excluded Medications List
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, perforated tympanic membrane or labyrinthitis, as identified by a general ear examination performed by medically qualified Investigators.
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.
Have had eye surgery within the previous three months or ear surgery within the previous six months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Investigational Treatment 2	Non-invasive brainstem stimulation	Investigational treatment mode (stimulation pattern) 2
Investigational Treatment 1	Non-invasive brainstem stimulation	Investigational treatment mode (stimulation pattern) 1

Primary Outcome Measures

Name	Time	Method
Change in The International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) Total Score	3 months	The MDS-NMS is a 52-item rater-administered scale used to assess a wide range of non-motor symptoms in Parkinson's disease. It measures both frequency (0/never to 4/ \>51% of the time) and severity (0/not present to 4/major distress or disturbance) of 13 domains (depression, anxiety, apathy, psychosis, impulse control/related disorders, cognition, orthostatic hypotension, urinary, sexual, gastrointestinal, sleep/wakefulness, pain, and other). Each question is scored by multiplying frequency x severity. All question scores for each domain are summed, and the scores for each domain are summed to provide the Total Score (range = 0-832) with the higher score indicating greater non-motor symptom burden. The higher the total score, the more progressed (i.e., worse) is the disease state. The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening.

Secondary Outcome Measures

Name	Time	Method
Change in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Parts I, II, and III Combined Score	3 months	The MDS-UPDRS evaluates motor (Parts 1 and III) and non-motor (Part II) experiences and complications of Parkinson's disease (PD) to characterizes the extent and burden of disease. Each question has five response options linked to accepted clinical terms: (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe)/evaluations and are divided across Part I (13 questions, 52 possible points), Part II (13 questions, 52 possible points), and Part III (33 questions based on 18 items, several with right, left or other body distribution scores, 132 possible points). The Combined Score is the sum of the points for all three Parts and ranges from 0 to 236. The higher the score, the more progressed (i.e., worse) is the disease state. The change/difference in scores between the baseline and end of study treatment are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.
Change in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II	3 months	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. The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. The more negative the change score, the greater the improvement.
Change From Baseline in the Clinical Global Impression-Improvement (CGI-I)	3 months	The Clinical Global Impression-Improvement (CGI-I) is a clinician outcome assessment used to assess 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. A 0 corresponds to no change, higher magnitude positive values correspond to greater improvements, and higher magnitude negative scores correspond to increased worsening. Scores range from -3 to +3 (-3 = very much worse, -2 = much worse, -1 = minimally worse, 0 = no change, 1=minimally improved, 2=much improved, 3=very much improved).
Change in the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale MDS-UPDRS Part III	3 months	The MDS-UPDRS Part III is a 33-item assessment of motor function evaluated by a trained, blinded rater. Each item has five response options linked to accepted clinical terms (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe) for a total scoring range of 0-132. Higher scores indicate more severe motor symptoms. The change/difference in scores between the baseline (average of Days 1 and 29) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.
Change From in the Parkinson's Disease Quality of Life Questionnaire Summary Index (PDQ-39 SI)	3 months	The PDQ-39 is a 39-item patient reported outcome questionnaire, which assesses Parkinson's disease-specific health related quality over the previous month. It includes 39 questions covering 8 dimensions: mobility (10), activities of daily living (6), emotional well-being (6), stigma (4), social support (3), cognition (4), communication (3), and bodily discomfort (3). Answers range from 0/never to 4/always. Each dimension is scored by summing the scores of each item, dividing that maximum possible score of all items in the dimension, and then multiplying by 100. The overall questionnaire score (the SI score) is the sum of all dimension scores divided by 8. Lower scores reflect better QoL. The change/difference in scores between the baseline (Days 1 and 29 average) and end of study treatment (Day 113) are reported. A positive change in scores indicates worsening. A negative change in scores indicates improvement.

Trial Locations

Locations (23): Movement Disorder Center of Arizona
🇺🇸
Scottsdale, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
CenExel Rocky Mountain Clinical Research
🇺🇸
Englewood, Colorado, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸
Boca Raton, Florida, United States
Headlands Research Orlando
🇺🇸
Orlando, Florida, United States
USF Parkinson's Disease and Movement Disorders Center
🇺🇸
Tampa, Florida, United States
University of Kansas Medical Center - Parkinson's Disease Center
🇺🇸
Kansas City, Kansas, United States
Quest Research
🇺🇸
Farmington Hills, Michigan, United States
Mercy Health Saint Mary's
🇺🇸
Grand Rapids, Michigan, United States
University of New Mexico
🇺🇸
Albuquerque, New Mexico, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
Meridian Clinical Research
🇺🇸
Raleigh, North Carolina, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Veracity Neuroscience
🇺🇸
Memphis, Tennessee, United States
Texas Movement Disorder Specialist
🇺🇸
Georgetown, Texas, United States
Houston Methodist Neurological Institute
🇺🇸
Houston, Texas, United States
Georgetown University
🇺🇸
McLean, Virginia, United States
Riverside Neurology Specialists
🇺🇸
Newport News, Virginia, United States
Inland Northwest Research
🇺🇸
Spokane, Washington, United States
King's College Hospital NHS Foundation Trust
🇬🇧
London, United Kingdom