The goal of this clinical trial is to evaluate the safety and tolerability of a novel deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM) to treat cognitive and cognitive-motor symptoms in individuals with Parkinson's disease. The main question it aims to answer is: Is a combined deep brain stimulation approach targeting the STN and NBM with four DBS leads safe and tolerable for cognitive and cognitive-motor symptoms in individuals with Parkinson's disease with Mild Cognitive Impairment. Ten participants are anticipated to be enrolled. Participants will undergo a modification of the traditional STN DBS approach for motor symptoms of PD. In addition to the two leads placed within the STN, two additional leads will be placed with the NBM for treatment of cognitive and cognitive-motor symptoms. Novel stimulation patterns will be used within the NBM to target cognitive and cognitive-motor symptoms using an investigational software. Participants will be followed over two years while receiving this therapy with assessments at baseline and every six months. Assessments will include a combination of neuropsychological evaluations, cognitive assessments, motor tasks (including gait/walking), and questionnaires to evaluate the treatment. Two different surgical trajectories will be used, with half the cohort randomized to each group. This will allow comparison of the impact of surgical trajectory on the intervention.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
10
This intervention is a 4-lead deep brain stimulation approach targeting the Subthalamic Nucleus (STN) and Nucleus Basalis of Meynert (NBM)
Stanford Neuroscience Health Center
Stanford, California, United States
RECRUITINGAdverse Events
Any untoward medical occurrence that occurs during this study whether or not considered related to the study device, study procedures, or study requirements that is identified or worsens during the duration of the study
Time frame: From baseline to 1 year into treatment
Swing Time Coefficient of Variation
Swing time variability will be measured using the dual force plates in the SIP task and IMUs for TBC. It is defined as the mean swing time coefficient of variation (CV) of both legs.
Time frame: From baseline to 1 year into treatment
Percent Time Freezing
Duration of freezing episodes during SIP will be measured using IMUs and force plates using a validated offline algorithm.
Time frame: From baseline to 1 year into treatment
Stride Time Coefficient of Variation
Stride time coefficient of variation will be measured using the dual force plates in the SIP task and IMUs. Stride time coefficient of variation is defined as the mean stride time coefficient of variation (CV) of both legs. A greater stride time CV is indicative of less rhythmic gait/stepping.
Time frame: From baseline to 1 year into treatment
Shank Angular Velocity
Shank angular velocity will be measured from IMUs work on the participant's leg/ankle. Reductions in this value are indicative of FOG and gait impairment.
Time frame: From baseline to 1 year into treatment
Tapping Speed
The interstrike-interval of alternating tapping will be measured using an engineered piano keyboard. A higher interstrike-interval indicates slower tapping
Time frame: From baseline to 1 year into treatment
Tapping Rhythmicity
The variability of the interstrike-interval of alternating tapping, as quantified by the coefficient of variation, will be measured using an engineered piano keyboard. A higher coefficient of variation indicates worse rhythmicity
Time frame: From baseline to 1 year into treatment
MDS-UPDRS III Score
PD symptoms will be assessed clinically using the MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Section III. This is a motor examination to evaluate speech, facial expression, tremor at rest, action or postural tremor of hands, rigidity, finger taps, hand movements, rapid alternating movement of hands, leg agility, arising from chair, posture, gait, freezing of gait, posture, body bradykinesia, and postural stability. Each item is scored on a scale from 0 (normal) to 4 (severe), with the total possible score ranging from 0 to 132.
Time frame: From baseline to 1 year into treatment
SAT Score
Each trial of the SAT will be categorized as a Hit (H), Miss (M), or False Alarm (FA). The SAT score is defined as ((H - FA) / \[2× (H + FA) - (H + FA)2\]), which ranges from - 1.0 (100% incorrect performance; all misses and false alarms) to +1.0 (100% correct performance; all hits and correct rejections).
Time frame: From baseline to 1 year into treatment
Percent False Positives
The percent of false positives during the SAT.
Time frame: From baseline to 1 year into treatment
Percent Misses
The percent of misses of total trials during the SAT
Time frame: From baseline to 1 year into treatment
Average + standard deviation of response time
The average and standard deviation of the response time during the SAT.
Time frame: From baseline to 1 year into treatment
Goal-directed focus of attention
Hit rate during the first minute in the no- distractor condition for the CTET.
Time frame: From baseline to 1 year into treatment
Sustained attention
Hit rate change slope in no-distractor condition for the CTET.
Time frame: From baseline to 1 year into treatment
Distractibility
Hit rate difference between no-distractor and distractor conditions for the CTET.
Time frame: From baseline to 1 year into treatment
Parkinson's Disease - Cognitive Rating Scale (PD-CRS)
Cognitive scale composed of 9 tasks that assesses the full range of cognitive dysfunction in PD. It is a scale of 0 to 134, with 134 being the best score.
Time frame: From baseline to 1 year into treatment
Montreal Cognitive Assessment (MoCA)
Total score to assess of this rapid screening test of different cognitive domains. It is a scale of 0 to 30, with 30 being the best score.
Time frame: From baseline to 1 year into treatment
Trails A
The time it takes to complete the task and errors.
Time frame: From baseline to 1 year into treatment
Trails B
The time it takes to complete the task and errors.
Time frame: From baseline to 1 year into treatment
Symbol Digit Modalities (SDMT) Oral and Written
The summation of the number of correct substitutions within the 90 second interval.
Time frame: From baseline to 1 year into treatment
visual puzzles from the Wechsler Adult Intelligence Scale-IV (WAIS-IV)
Percentile of performance on visual puzzles for participant's demographic.
Time frame: From baseline to 1 year into treatment
Judgement of Line Orientation
Percentile of performance on judgement of line orientation for participant's demographic.
Time frame: From baseline to 1 year into treatment
Patient Health Questionnaire-9 (PHQ-9)
Total score on questionnaire regarding participant's mood the last 2 weeks. The scale ranges from 0 to 27 with a score of 27 indicating the most severe symptoms.
Time frame: From baseline to 1 year into treatment
General Anxiety Disorder-7 (GAD-7)
Total score on questionnaire regarding participant's anxiety the last two weeks.The scale ranges from 0 to 21 with a score of 21 indicating the most severe symptoms.
Time frame: From baseline to 1 year into treatment
MDS-UPDRS I
Total score evaluating the non-motor aspects of experiences of daily living. It is a scale from 0 to 52 with 52 being the most severe symptoms.
Time frame: From baseline to 1 year into treatment
MDS-UPDRS II
Total score evaluating the motor aspects of experiences of daily living. It is a scale from 0 to 52 with 52 being the most severe symptoms.
Time frame: From baseline to 1 year into treatment
MDS-UPDRS IV
Total score of motor complications experienced by the participant. It is a scale from 0 to 24 with 24 being the most severe symptoms.
Time frame: From baseline to 1 year into treatment
Neuropsychiatric Inventory (NPI)
Total score for symptom severity and distress via questionnaire. It is a scale from 0 to 60 with 60 indicating worse symptoms.
Time frame: From baseline to 1 year into treatment
Parkinson's Disease Questionnaire-39 (PDQ-39)
Total score for Parkinson's disease-specific health related quality over the last month across 8 quality of life dimensions assessed via questionnaire. Score ranges from 0 to 100 with 100 indicating more symptoms and problems.
Time frame: From baseline to 1 year into treatment
Caregiver Burden Assessment
Total score on caregiver self-report to assess the stress-levels of family caregivers. It is a scale from 0 to 88 with higher scores indicating greater or worse burden.
Time frame: From baseline to 1 year into treatment
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