STEM-PD Open Label Extension (OLE)

Not Applicable

Terminated

Conditions: Parkinson Disease
Parkinson's Disease and Parkinsonism

Registration Number: NCT04799418

Lead Sponsor: Scion NeuroStim

Brief Summary: This study seeks to establish the safety and efficacy of extended twice daily time-varying caloric vestibular stimulation treatments for treating symptoms associated with Parkinson's disease. Only participants who completed the STEM-PD randomized controlled trial portion (NCT04797611) are eligible to participate in the open label extension portion.

Detailed Description: Up to 220 participants will enter an open label extension study during which all study participants will receive active (i.e., time-varying caloric vestibular stimulation) treatment for 12 weeks (84 days). Study participants will be followed for 16 weeks (112 days) post treatment-cessation and then the twice daily active treatments will be re-introduced for the final 8 weeks (56 days).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 148

Inclusion Criteria

Completion of the study activities in the STEM-PD RCT trial (see STEM-PD RCT eligibility criteria noted below).
Participants must be willing and able to give consent to participate in the study trial.
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 first three months of the OLE (Day197).

Exclusion Criteria

Participant anticipates being unable to attend all visits and complete all study activities.
Has a planned surgery scheduled to occur during the first 90 days of the OLE that would typically be followed with a prescription for pain management

STEM-PD RCT Eligibility criteria:

Inclusion:

Adult participants (aged 18 - 85 years inclusive).
Have been diagnosed with PD according to the UK Brain Bank Criteria (allowing for an exclusion in Step 2 for "more than one affected relative").
Participants must have demonstrated a sustained positive response to 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 reports limitation 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.).
Participants must be able and willing to consent to participate in the study for the RCT and OLE.
Participants must be willing and able to comply with study requirements.
Participants must have at minimum a moderate burden of NMS (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.
Must have a study partner (defined as someone who sees the participant for more than one hour a day, 3x per week) that is willing to consent and participate in the trial.
Participants must have capabilities to use and access smartphones 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:

Women of child-bearing potential who are pregnant or plan to become pregnant during the course of the study

• Women of child-bearing potential (i.e., are not yet either 3 years removed from their first menopausal symptom or 12 months removed from last menses), 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 listed in section 5.3.3 for the entirety of the RCT and OLE;
Have a history or prior diagnosis of dementia 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 (TIA) within 6 months.
Are receiving deep brain stimulation therapy.
Are treated with a pump for continuous delivery of dopamine replacement therapy.
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.
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 tinnitus 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 sequela.
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Change From Baseline in The International Parkinson and Movement Disorder Society - Non-Motor Rating Scale (MDS-NMS) Total Score	3 months (NCT04797611 RCT: Day 29 - Day 113; This OLE: Day 113 to Day 197)	The primary endpoint is the change in MDS-NMS total score during the first treatment period during the open label extension (OLE) relative to the score at the end of the NCT04797611 randomized controlled trial (RCT) treatment period (day 113) for the passive-active treatment group compared to the change in MDS-NMS total score during the RCT treatment period relative to the pretreatment baseline. The MDS-NMS is 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. 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II	3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197)	The MDS-UPDRS Part II is a 13-item patient-reported assessment of activities 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. This secondary endpoint evaluates the change in the MDS-UPDRS Part II score obtained during the first treatment period of this open label extension (OLE) relative to the score obtained at the end of the NCT04797611 randomized controlled trial (RCT) period (day 113).
Change From Baseline in the Parkinson's Disease Quality of Life Questionnaire Summary Index (PDQ-39 SI)	3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197	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 covering: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items), and bodily discomfort (3 items). Answers for each item 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 total score (the SI score) is the sum of all dimension scores divided by 8 and ranges from 0-100, the higher the total score the greater the health problems). This endpoint compares the change in the PDQ-39 total score taken at the end of the RCT treatment period to the total score obtained during the OLE's first treatment period.
Change From Baseline in the Combined Measure of The International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Parts I, II and III	3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197	The MDS-UPDRS evaluates motor (Parts I 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 more negative the change score the greater the symptomatic improvement.
Change From Baseline in the Clinical Global Impression - Improvement (CGI-I)	RCT: from Baseline (Day 29) up to 3 months (Day 113); OLE: from Baseline (Day 29) up to 11 months (Day 365)	The CGI-I is a clinician assessment the extent of clinically meaningful change that has occurred in the patient's illness at day 197/365 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 From Baseline in the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination (MDS-UPDRS Part III)	3 months (NCT04797611 RCT: Day 29 - Day 113; this OLE: Day 113 to Day 197)	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. This secondary endpoint evaluates the change in MDS-UPDRS Part III score during the first treatment period of this open label extension (OLE) relative to the score at the end of the NCT04797611 randomized controlled trial (RCT) treatment period (day 113) for the passive-active treatment group compared to the change in MDS-UPDRS Part III score during the RCT treatment period relative to the pre-treatment baseline.

Trial Locations

Locations (15): Movement Disorder Center of Arizona
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Scottsdale, Arizona, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Parkinson's Disease and Movement Disorder of Boca Raton
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Boca Raton, Florida, United States
Headlands Research Orlando
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Orlando, Florida, United States
University of South Florida
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Tampa, Florida, United States
University of Kansas Medical Center - Parkinson's Disease Center
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Kansas City, Kansas, United States
Quest Research
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Farmington Hills, Michigan, United States
Mercy Health Saint Mary's
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Grand Rapids, Michigan, United States
University of New Mexico
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Albuquerque, New Mexico, United States
Meridian Clinical Research
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Raleigh, North Carolina, United States
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Movement Disorder Center of Arizona
🇺🇸Scottsdale, Arizona, United States