Parkinson Disease Dementia
Conditions
Keywords
medical device, Non-Invasive Brain Stimulation, neuromodulation
Brief summary
The purpose of this single arm study is to evaluate the feasibility and safety of treatments with a non-invasive neuromodulation device in adults diagnosed with mild/moderate Parkinson's disease dementia (PDD). A non-invasive device is a device that stays outside of the body and is not implanted and does not penetrate the skin. Neuromodulation means that the device stimulates activity in the brain.
Detailed description
Up to 12 participants will self-administer treatments twice daily in the home setting over a period of 12 weeks. There are 4 study center visits, including an eligibility visit, as well as multiple phone calls.
Interventions
Study participants will self-administer \ 19-minute treatments twice daily in the home setting over 12 weeks using a non-invasive brainstem modulation device.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Scion NeuroStim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults, age 50 years of older, diagnosed with Clinically Established or Clinically Probable Parkinson's disease according to the MDS Clinical Diagnostic Criteria * Participants with a clinical diagnosis of probable Parkinson's disease dementia ( PDD) using criteria defined in Emre et al., 2007 and in accordance with procedures defined in Dubois et al., 2007 (allowing for diagnosis of PD defined in Step 1 to be according to MDS Clinical Diagnostic criteria instead of the Queen Square Brain Bank Criteria) * Participants must be able and willing to consent to participate in the study and comply with all study requirements. If the participant is unable to consent due to limited capacity, a Legally Authorized Representative (LAR) must consent. * 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 and not to introduce new medications used to treat PD (motor or non-motor symptoms) during the study. * The principal investigator, or designee, must have confidence in the participant's ability to reliably use the TNM™ device, and to understand and complete the assessments (provided in English only) within a given on-state. * Participant must have a study partner (defined as someone who sees the participant for more than three hours a day, 5 times per week) that is willing to consent and participate in the trial.
Exclusion criteria
* Participant anticipates being unable to attend all visits and complete all study activities during the trial. * Women of child-bearing potential who are pregnant or plan to become pregnant during the course of the trial * Has any significant co-morbidity/condition, planned surgery or participation in another clinical trial which may either prevent safe participation in the study procedures or interfere with the evaluation of safety or efficacy of the study Device as a potential treatment for PDD * In the Investigator's opinion, has severe dementia, (e.g., Mini Mental State Exam score (at screen visit) \<15 and/or requires significant assistance with activities of daily living due to cognitive deficits) * Has experienced a myocardial infarction, angina, or stroke within the past 12 months, transient ischemic attack (TIA) within the past 6 months or has a documented aspiration event in the medical records * Are receiving late-stage therapies for PD (e.g., deep brain stimulation or pump infusion therapies) or are being treated with another neurostimulation device * History of interventional brain surgery or have received magnetic resonance guided high intensity focused ultrasound * Demonstrate suicidality at screening (scores ≥ 4 on the Columbia- Suicide Severity Rating Scale Baseline In the past Month section) * 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 * Have active ear infections, perforated tympanic membrane or labyrinthitis, as identified by a general ear examination * Use any drugs excluded in the Excluded Medications List * Use of antipsychotic medication(s) listed in the Approved Concomitant Medications (i.e., pimavanserin and quetiapine) that have not been taken for more than 180 days and does not have medical record documentation of normal QTc interval (i.e., no prolongation of the QTc interval) as measured via electrocardiogram after starting the medication * Have active ear infections, perforated tympanic membrane or labyrinthitis, as identified by a general ear examination performed by medically qualified Investigators or have chronic tinnitus that has been ongoing for at least 3 months * Have a cochlear implant, myringotomy tubes or hearing aids that cannot be easily/reliably removed for treatment * Clinically significant abnormalities in B12, thyroid function, blood count, comprehensive metabolic panel or urinalysis results tested at the study screen. Screening tests are not required in cases where test results within normal range within 6 months of study screen are documented in the medical records.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MDS-UPDRS (Sum of Parts I, II & III) | 12 weeks | Parts I, II, and III of the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates motor (Parts I and III) and non-motor (Part II) experiences and complications of Parkinson's disease (PD) by which it characterizes the extent and burden of disease. Questions/evaluations are divided across Part I (13 questions, 52 possible points), Part II (13 questions, 52 possible points), Part III (33 questions based on 18 items, several with right, left or other body distribution scores, 132 possible points) and summed. Each question has five response options linked to accepted clinical terms (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe) for a total possible score of 236. The change between baseline and Day 84 is reported. A positive change in scores between baseline to Day 84 indicates symptom/disease worsening. A negative change in score between baseline and Day 84 indicates symptom/disease improvement. |
| Feasibility of Neuromodulation Device Use in PDD Population, Part 1 | 12 weeks | Retention rate or the percent of participants that complete the secondary endpoint (MoCA) at all study visits in the study protocol during the 12-week treatment period. High retention: \>90%, Moderate retention: 60-90 %, Low retention:\< 60 % |
| Feasibility of Neuromodulation Device Use in PDD Population, Part 2 | 12 weeks | Treatment adherence rate during the 12-week treatment period. High adherence: \>84%, Moderate adherence: 55-84 %, Low adherence: \< 55 % |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montreal Cognitive Assessment (MoCA) | 12 weeks. | The MoCA assesses cognition over 6 domains: Memory, Executive function, Attention, Language, Visuospatial, and Orientation. Points across all 6 domains are summed, and this sum equals the total score (min 0 - max 30). A higher total score indicates better cognitive function; a positive score for difference in points indicates improvement. A total score of 26-30 reflects normal cognition. Mild cognitive impairment is associated with a total score of 18-25. Total scores of 10 - 17 indicate moderate cognitive impairment; a total score less than 10 shows severe cognitive impairment. The change (difference) in the Montreal Cognitive Assessment (MoCA) total score taken at baseline and, again, at the end of treatment visit (Day 84) after 12 weeks of treatment is reported. A positive change in scores indicates improvement; whereas, a negative change in scores between baseline and Day 84 indicates worsening. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Investigational Treatment Time-varying caloric vestibular stimulation | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Study Termination | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Investigational Treatment |
|---|---|
| Age, Continuous | 75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| MDS-UPDRS (Sum of Parts I, II, and III) | 76 Total points |
| Montreal Cognitive Assessment (MoCA) | 18 Total points |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 9 |
| other Total, other adverse events | 4 / 9 |
| serious Total, serious adverse events | 2 / 9 |
Outcome results
Primary
Feasibility of Neuromodulation Device Use in PDD Population, Part 1
Retention rate or the percent of participants that complete the secondary endpoint (MoCA) at all study visits in the study protocol during the 12-week treatment period. High retention: \>90%, Moderate retention: 60-90 %, Low retention:\< 60 %
Time frame: 12 weeks
Population: Enrolled participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Treatment | Feasibility of Neuromodulation Device Use in PDD Population, Part 1 | 3 Participants |
Primary
Feasibility of Neuromodulation Device Use in PDD Population, Part 2
Treatment adherence rate during the 12-week treatment period. High adherence: \>84%, Moderate adherence: 55-84 %, Low adherence: \< 55 %
Time frame: 12 weeks
Population: Participants for whom study devices that had been received by the Sponsor prior to study termination allowing for study device data download.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Investigational Treatment | Feasibility of Neuromodulation Device Use in PDD Population, Part 2 | 95.4 percentage of treatment adherence |
Primary
MDS-UPDRS (Sum of Parts I, II & III)
Parts I, II, and III of the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) evaluates motor (Parts I and III) and non-motor (Part II) experiences and complications of Parkinson's disease (PD) by which it characterizes the extent and burden of disease. Questions/evaluations are divided across Part I (13 questions, 52 possible points), Part II (13 questions, 52 possible points), Part III (33 questions based on 18 items, several with right, left or other body distribution scores, 132 possible points) and summed. Each question has five response options linked to accepted clinical terms (0/normal, 1/slight, 2/mild, 3/moderate, and 4/severe) for a total possible score of 236. The change between baseline and Day 84 is reported. A positive change in scores between baseline to Day 84 indicates symptom/disease worsening. A negative change in score between baseline and Day 84 indicates symptom/disease improvement.
Time frame: 12 weeks
Population: Participants that completed an end of treatment visit or early termination visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Investigational Treatment | MDS-UPDRS (Sum of Parts I, II & III) | -2 # of points difference |
p-value: 0.8125Wilcoxon matched-pairs signed rank
Secondary
Montreal Cognitive Assessment (MoCA)
The MoCA assesses cognition over 6 domains: Memory, Executive function, Attention, Language, Visuospatial, and Orientation. Points across all 6 domains are summed, and this sum equals the total score (min 0 - max 30). A higher total score indicates better cognitive function; a positive score for difference in points indicates improvement. A total score of 26-30 reflects normal cognition. Mild cognitive impairment is associated with a total score of 18-25. Total scores of 10 - 17 indicate moderate cognitive impairment; a total score less than 10 shows severe cognitive impairment. The change (difference) in the Montreal Cognitive Assessment (MoCA) total score taken at baseline and, again, at the end of treatment visit (Day 84) after 12 weeks of treatment is reported. A positive change in scores indicates improvement; whereas, a negative change in scores between baseline and Day 84 indicates worsening.
Time frame: 12 weeks.
Population: Participants that completed the MoCA at the End of Treatment visit (day 84) or early termination visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Investigational Treatment | Montreal Cognitive Assessment (MoCA) | 0 # of points difference |
p-value: >0.9999Wilconxon matched-pairs signed rank test