Clinical trial NCT04797611: STEM-Parkinson's Disease
Official title: Non-Invasive Brainstem Modulation for the Treatment of Non-Motor Symptoms in Parkinson's Disease: A Randomized Controlled Trial (RCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Parkinson's Disease and Parkinsonism
Keywords: Randomized Controlled Trial (RCT)
Medical Devices
Non-Motor Symptoms (NMS)
Non-Invasive Brain Stimulation
tvCVS
Lead sponsor: Scion NeuroStim
Sponsor class: INDUSTRY
First posted: 2021-03-15
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in The International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) Total Score
timeFrame: 3 months
Secondary outcomes:
measure: Change in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Parts I, II, and III Combined Score
timeFrame: 3 months
measure: Change in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II
timeFrame: 3 months
measure: Change From Baseline in the Clinical Global Impression-Improvement (CGI-I)
timeFrame: 3 months
measure: Change in the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale MDS-UPDRS Part III
timeFrame: 3 months
measure: Change From in the Parkinson's Disease Quality of Life Questionnaire Summary Index (PDQ-39 SI)
timeFrame: 3 months
Other outcomes:
measure: Change in the Mini-Balance Evaluation Systems Test (Mini BESTest)
timeFrame: 3 months
measure: Change in the Montreal Cognitive Assessment (MoCA)
timeFrame: 3 months
measure: Change in the Oral Symbol Digit Modality Test (Oral SDMT)
timeFrame: 3 months
measure: Change in the Parkinson's Disease Sleep Scale 2 (PDSS 2)
timeFrame: 3 months
measure: Change in Epworth Sleepiness Scale (ESS)
timeFrame: 3 months
measure: Change in the Parkinson Anxiety Scale (PAS)
timeFrame: 3 months
measure: Change in the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue)
timeFrame: 3 months
measure: Change in the Geriatric Depression Scale-15 (GDS-15)
timeFrame: 3 months
measure: Change in the Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) Non-Motor Fluctuations (NMF) Subscale Score
timeFrame: 3 months
measure: Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV
timeFrame: 3 months
measure: Change in the Zarit Burden Interview (ZBI)
timeFrame: 3 months
measure: Change in the Patient Reported Outcome - Parkinson's Disease (PRO-PD)
timeFrame: 3 months
measure: Change in The Modified Schwab and England Activities of Daily Living Scale
timeFrame: 3 months
measure: Change in EncephaLog™ 3 Meter Timed Up and Go (TUG) Test
timeFrame: 3 months
measure: Change in EncephaLog™ Finger Tapping Test
timeFrame: 3 months
measure: Change in EncephaLog™ 10 Meter Timed Up and Go (TUG) Test
timeFrame: 3 months
measure: Change in Unified Parkinson's Disease Rating Scale Part I (UPDRS I)
timeFrame: 3 months
measure: Change in Hoehn & Yahr (H&Y)
timeFrame: 3 months
measure: Change in International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS I) Score
timeFrame: 3 months
Locations:
city: Scottsdale
country: United States
facility: Movement Disorder Center of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Orlando
country: United States
facility: Headlands Research Orlando
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorders Center
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center - Parkinson's Disease Center
state: Kansas
city: Farmington Hills
country: United States
facility: Quest Research
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Raleigh
country: United States
facility: Meridian Clinical Research
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Veracity Neuroscience
state: Tennessee
city: Georgetown
country: United States
facility: Texas Movement Disorder Specialist
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: McLean
country: United States
facility: Georgetown University
state: Virginia
city: Newport News
country: United States
facility: Riverside Neurology Specialists
state: Virginia
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
References: