Biomarkers to Guide Directional DBS for Parkinson's Disease

Noninvasive Biomarkers to Advance Emerging DBS Electrode Technologies in Parkinson's Disease (SUNDIAL, SUbthalamic Nucleus DIrectionAL vs Circular Stimulation Study)

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03353688

Enrollment

Registered

2017-11-27

Start date

2017-11-03

Completion date

2024-07-31

Last updated

2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Keywords

Parkinson's, Parkinson Disease

Brief summary

The purpose of this study is to investigate the clinical efficacy of directional DBS electrode technology and whether electrophysiology biomarkers can predict effective contact segments for chronic therapy.

Detailed description

Although deep brain stimulation (DBS) can be remarkable for treating symptoms of Parkinson's disease, improvement varies across clinical trials, individual patients, and over time. A major limitation to the advancement of DBS therapy is that there are no established biomarkers to tailor stimulator settings in individuals. Emerging segmented (directional) lead technology allows current steering, a new opportunity to improve tolerability and efficacy by shaping the DBS electrical field. This novel lead design has 8 contacts rather than the 4 available with currently available leads. How do the investigators optimally adjust stimulation parameters when there are far more potentially useful settings than can be practically evaluated in clinic? How do the investigators know that DBS settings in a given patient are optimal or appropriate? The investigators have pioneered minimally invasive, rapidly acquired biomarkers to solve these important problems. Using electrocorticography, electroencephalography, and subcortical local field potentials, the investigators will measure whether resting or stimulus-evoked electrophysiology can serve as a predictive biomarker to guide activation and adjustment of a directional DBS system. The purpose of this randomized, double-blind crossover study is to measure the clinical efficacy of directional versus omnidirectional stimulation and to explore whether electrophysiology biomarkers can rapidly predict effective, well-tolerated contacts for directional DBS therapy.

Interventions

DEVICEBoston Scientific Vercise PC IPG with directional DBS lead

Deep brain stimulation

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

This is a triple blind study. Participants, raters, and investigator are masked to the assignment of directional versus omnidirectional unilateral subthalamic deep brain stimulation guided by behavioral programming for Parkinson's disease with motor fluctuations. For the nested exploratory arm evaluating directional DBS guided by electrophysiology biomarkers, the study is double-blind (investigator is not blinded).

Intervention model description

This is a triple blind, randomized crossover study of directional versus omnidirectional unilateral subthalamic deep brain stimulation for Parkinson's disease with motor fluctuations.

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

1. Age ≥18 years and ≤70 years. 2. Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PD features (tremor, rigidity, or bradykinesia). 3. Disease duration of 4 years or more. 4. Participant has elected to undergo DBS surgery as part of routine care, and the subthalamic nucleus (STN) is recommended as the surgical target. 5. Participant agrees to not undergo contralateral DBS for the other side of the brain until ≥ 12 months after initial DBS surgery. 6. Participant is healthy enough to undergo surgery and the research protocol. 7. Normal, or essentially normal, preoperative brain MRI. 8. Willingness and ability to cooperate during awake DBS surgery, as well as during post-operative evaluations, adjustments of medications and stimulator settings. 9. Participant's health insurance and/or Medicare covers DBS surgery as part of routine care. 10. Refractory motor symptoms such as tremor, dyskinesias, wearing off, and/or motor fluctuations, causing significant disability or occupational dysfunction, despite reasonable attempts at medical management, as determined by our consensus DBS committee. 11. Stable doses of PD medications for at least 28 days prior to baseline assessments. 12. Improvement of motor signs ≥30% with dopaminergic medication as assessed with the use of the Movement Disorders - Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III; scores range from 0 to 108, with higher scores indicating worse functioning). 13. Disease severity ratings above Hoehn and Yahr stage 1, defined as unilateral involvement only with minimal or no functional disability, with scores ranging from 0 to 5 and higher scores indicating more severe disease. 14. Score of more than 6 for activities of daily living in the worst off medication condition despite medical treatment, as assessed with the use of the MDS-UPDRS II (scores range from 0 to 52, with higher scores indicating worse functioning), or mild-to-moderate impairment in social and occupational functioning (score of 51 to 80% on the Social and Occupational Functioning Assessment Scale with scores ranging from 1 to 100 and lower scores indicating worse functioning). 15. Dementia Rating Scale-2 (DRS-2) score of ≥130 on medications. 16. Beck Depression Inventory II (BDI-II) score of ≤25 on medications. 17. Participant expresses understanding of the consent process, terms of the study protocol, is available for follow-up over the length of the study, and signs informed consent.

Exclusion criteria

1. Age \<18 years or \>70 years. 2. Participant's insurance will not cover the costs of surgery with the investigational device. 3. Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions contraindicating DBS surgery or stimulation. 4. Duration of disease of \<4 years 5. Participant or care team determine that contralateral DBS for the other side of the brain will likely be clinically indicated \<12 months after initial DBS surgery. 6. Diagnosis or suspicion of atypical parkinsonism (progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome) or drug-induced parkinsonism, or significant neurological disease other than Parkinson's disease. 7. Disease severity ratings of Hoehn and Yahr stage 1, defined as unilateral involvement only with minimal or no functional disability, with scores ranging from 0 to 5 and higher scores indicating more severe disease. 8. Diagnosis of psychogenic movement disorder based on consensus criteria. 9. Score of \>25 on the Beck Depression Inventory II, with scores ranging from 0 to 63 and higher scores indicating worse functioning), or history of suicide attempt. 10. Any current acute psychosis, alcohol abuse or drug abuse. 11. Clinical dementia (score of ≤130 on the Mattis Dementia Rating Scale with scores ranging from 0 to 144 and higher scores indicating better functioning). 12. Ongoing or pervasive impulse control disorder not resolved by reduction of dopaminergic medications. 13. Use of anticoagulant medications that cannot be discontinued during perioperative period. 14. History of hemorrhagic stroke. 15. Current or future risk of immunocompromise that might significantly increase risk of infection. 16. History of recurrent of unprovoked seizures. 17. Lack of clear levodopa responsiveness. 18. Any medical condition requiring repeated MRI. 19. The presence of an implanted device (e.g., cochlear implant, pacemaker, neurostimulators), whether turned on or off. 20. Prior DBS surgery or ablation within the affected basal ganglion. 21. A condition requiring or likely to require the use of diathermy. 22. Structural lesions such as basal ganglionic stroke, tumor or vascular malformation as etiology of the movement disorder. 23. Any medical or psychological problem that would interfere with the conduction of the study protocol 24. A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception.

Design outcomes

Primary

Measure	Time frame	Description
Change From Preoperative Baseline in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS Part III) Off Medications	2, 4, and 6 months post op	A blinded examiner will measure Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 motor scores off medications. MDS-UPDRS Part III is a motor examination consisting of 18 summed items where the investigator rates the severity of Parkinson's motor symptoms based on a scale of 0 - 4. Higher values indicate worse function (possible min score = 0, possible max score = 72). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Treatment Preference Survey Programming Strategy Preference	4 months post surgery	Based on overall quality of life, participants will select their preference between directional and omnidirectional DBS.

Secondary

Measure	Time frame	Description
Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Delayed Recall Raw Score (Versions AB, CD, CR, GE)	2, 4, and 6 months post op	The Auditory Verbal Learning Test (AVLT) delayed recall raw score (versions AB, CD, CR, GE) evaluates a person's ability to encode, consolidate, store, and retrieve verbal information. Participants are read a list of 12 words and later asked to recall the items on the list. Scores indicate the number of items recalled. Higher values indicate better function (possible min score = 0, possible max score = 12). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Recognition Raw Score (Versions AB, CD, CR, GE)	2, 4, and 6 months post op	The Auditory Verbal Learning Test (AVLT) Recognition Raw Score (versions AB, CD, CR, GE) evaluates a person's ability to encode, consolidate, store, and retrieve verbal information. Participants are given a list of 15 target words. The list is taken away and each is asked to now pick out the 15 target words from a larger list of 30 words. Scores indicate the overall number of target words correctly recognized (minimum = 0, maximum = 15). Higher scores indicate better performance. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Learning Raw Score (Versions AB, CD, CR, GE)	2, 4, and 6 months post op	The AVLT (versions AB, CD, CR, GE) evaluates a person's ability to encode, consolidate, store, and retrieve verbal information. Participants are read a list of 12 words and asked to immediately recall the items on the list over 6 separate trials. Scores indicate the number of items recalled. Higher values indicate better function (possible min score = 0, possible max score = 72). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Letter Fluency Test Raw Score (Version: CFL, FAS)	2, 4, and 6 months post op	The Letter Fluency Test (version: CFL, FAS) evaluates the number of words beginning with the letters C, F, L, A, and S that a participant can produce in one minute (minimum = 0, maximum = infinity). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Voice Handicap Index	2, 4, and 6 months post op	The Voice Handicap Index evaluates speech function with a 30-item self-administered questionnaire that asks participants to describe their voice and the effects of their voice on their lives. Participants respond on a 0 - 4 scale (minimum = 0, maximum = 120. Higher scores indicate worse functiion. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Communicative Participation Item Bank (CPIB)	2, 4, and 6 months post op	The Communicative Participation Item Bank (CPIB) evaluates the extent to which communication disorders interfere with communicative participation. Participants respond on a 0 - 3 scale (minimum = 0, maximum = 30). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the 9-Hole Pegboard Test	2, 4, and 6 months post op	The 9-Hole Pegboard Test evaluates one's upper extremity motor function. It is a timed test in which participants place 9 pegs in a pegboard and then remove them. Faster times indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Gait Initiation Test	2, 4, and 6 months post op	The gait initiation test evaluates the phase between standing motionless and steady-state locomotion. This is a timed test in which participants are given a go signal and the time until first stride is recorded. Faster times indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Stepping Thresholds Test	2, 4, and 6 months post op	The stepping thresholds test evaluates a person's compensatory stepping thresholds. This is a test in which the floor surface is unexpectedly moved beneath a participant. The distance a participant moves their feet in order to compensate is recorded. The smaller displacement scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Quiet Stance Measure	2, 4, and 6 months post op	The quiet stance measure evaluates a person's postural control during quiet standing. This is a measure of sway distance. Lower scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Parkinson's Disease Quality of Life	2, 4, and 6 months post op	The Parkinson's Disease Quality of Life (PDQ-8) evaluates overall health status. It consists of eight questions regarding mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort. Participants choose answers on a scale ranging from never (0) to always (4) (minimum = 0, maximum = 32). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the the Neuro-QOL Item Bank v1.0 Positive Affect and Well-Being Short Form	2, 4, and 6 months post op	The Neuro-QOL Item Bank v1.0 Positive Affect and Well-Being Short Form evaluates feelings that reflect a level of general satisfaction with life as well as a sense that life has purpose and meaning. Participants respond to questions on a 1-5 scale (minimum = 9, maximum = 45). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.1 Satisfaction With Social Roles and Activities Short Form	2, 4, and 6 months post op	The Neuro-QOL Item Bank v1.1 Satisfaction with Social Roles and Activities short form short form evaluates one's satisfaction and discontentment with performing usual social roles and activities. Participants respond to questions on a 1-5 scale (minimum = 8, maximum = 40). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Item Bank v2.0 Cognitive Function Short Form	2, 4, and 6 months post op	The Neuro-QOL Item Bank v2.0 Cognitive Function short form evaluates mental acuity, concentration, verbal and nonverbal memory, verbal fluency, and perceived changes in these cognitive functions. Participants respond to questions on a 1-5 scale (minimum = 8, maximum = 40). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 Lower Extremity Function (Mobility) Short Form	2, 4, and 6 months post op	The Neuro-QOL Item Bank v1.0 Lower Extremity Function (Mobility) short form evaluates functioning of one's lower extremities. Participants respond to questions on a 1-5 scale (minimum = 8, maximum = 40). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 Upper Extremity Function (Fine Motor, ADL) Short Form	2, 4, and 6 months post op	The Neuro-QOL Item Bank v1.0 Upper Extremity Function (Fine Motor, ADL) short form evaluates functioning of one's upper extremity function in fine motor and ADL capabilities. Participants respond to questions on a 1-5 scale (minimum = 9, maximum = 45). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 Stigma Short Form	2, 4, and 6 months post op	The Neuro-QOL Item Bank v1.0 Stigma short form evaluates one's sensitivity of illness-related stigma. Participants respond to questions on a 1-5 scale (minimum = 8, maximum = 40). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Beck Depression Inventory-2 (BDI-2)	2, 4, and 6 months post op	The Beck Depression Inventory-2 is a 21 question self-report inventory which evaluates a person's severity of depression. Items are answered on a 0 - 3 scale. Higher values indicate worse function (possible min score = 0, possible max score = 63). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 Emotional and Behavioral Dyscontrol Short Form	2, 4, and 6 months post op	Neuro-QOL Item Bank v1.0 Emotional and Behavioral Dyscontrol short form evaluates one's confidence to manage/control symptoms of frustration, disappointment, anger, and other negative emotions. Participants respond to questions on a 1-5 scale (minimum = 8, maximum = 40). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 Global Health Short Form	2, 4, and 6 months post op	The PROMIS v1.0 Global Health short form evaluates the individual's global health. This is a 10 question scale on which 9 of the questions are answered with a 1 - 5 score. The remaining item is answered with a 0 - 10 score. (minimum = 9, maximum = 55). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health Mental Health Score	2, 4, and 6 months post op	The (PROMIS) Scale v1.2 Global Health evaluates one's overall physical and mental health. This is a 10 item scale with scores ranging from 4-20. Higher scores indicate better overall health. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v2.0 Ability to Participate in Social Roles and Activities Short Form	2, 4, and 6 months post op	The PROMIS v2.0 Ability to Participate in Social Roles and Activities short form evaluates one's perceived ability to perform one's usual social roles and activities. This is an 8 question measure and answers are given on a 1 - 5 scale (minimum = 8, maximum = 40). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 Emotional Distress - Anxiety Short Form	2, 4, and 6 months post op	The PROMIS v1.0 Emotional Distress - Anxiety short form evaluates one's feelings of anxiety, such as fear and worry. This is a 7 item scale and participants answer with a 1 - 5 score for each item (minimum = 7, maximum = 35). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 Emotional Distress - Depression Short Form	2, 4, and 6 months post op	The PROMIS v1.0 Emotional Distress - Depression short form evaluates one's feelings of negative mood and depression. This is an 8 item scale and participants answer with a 1 - 5 score for each item (minimum = 8, maximum = 40). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v2.0 Physical Function Short Form	2, 4, and 6 months post op	The PROMIS v2.0 Physical Function short form measures self-reported capability rather than actual performance of physical activities. This is a 10 item scale and participants answer with a 1 - 5 score for each item (minimum = 10, maximum = 50). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 Fatigue Short Form	2, 4, and 6 months post op	The PROMIS v1.0 Fatigue short form evaluates one's range of symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. This is a 6 item scale and participants answer with a 1 - 5 score for each item (minimum = 6, maximum = 30). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement	2, 4, and 6 months post op	The PROMIS v1.0 Pain Interference short form evaluates the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. This is a 6 item scale and participants answer with a 1 - 5 score for each item (minimum = 6, maximum = 30). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 Sleep Disturbance Short Form	2, 4, and 6 months post op	The PROMIS v1.0 Sleep Disturbance short form evaluates one's perceptions of sleep quality. This is an 8 item scale and participants answer with a 1 - 5 score for each item (minimum = 8, maximum = 40). Higher scores indicate worse function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery Dimensional Change Card Sort Score	2, 4, and 6 months post op	The NIH Toolbox Cognition Battery evaluates cognitive function with Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Picture Vocabulary Test, Pattern Comparison Processing Speed Test, Picture Sequence Memory Test, and Oral Reading Recognition. On this test participants are asked to match pictures to a category and receive one point for each correct match (minimum = 0, maximum = 40). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery Flanker Test Score	2, 4, and 6 months post op	The NIH Toolbox Cognition Battery evaluates cognitive function with Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Picture Vocabulary Test, Pattern Comparison Processing Speed Test, Picture Sequence Memory Test, and Oral Reading Recognition. The Flanker Test is a test in which participants are asked to focus on a particular stimulus while inhibiting attention to another. An accuracy score is derived by calculating (Accuracy Score = 0.125 \* Number of Correct Responses) (minimum=0, maximum=5). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery List Sorting Working Memory Test Score	2, 4, and 6 months post op	The NIH Toolbox Cognition Battery evaluates cognitive function with Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Picture Vocabulary Test, Pattern Comparison Processing Speed Test, Picture Sequence Memory Test, and Oral Reading Recognition. The list sorting working memory test is a test in which lists of items are presented and participants are asked to recall items from the list in a particular order. Scoring is done based on the number of items correctly recalled and sequenced (minimum = 0, maximum = 26). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery Oral Reading Test Score	2, 4, and 6 months post op	The NIH Toolbox Cognition Battery evaluates cognitive function with Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Picture Vocabulary Test, Pattern Comparison Processing Speed Test, Picture Sequence Memory Test, and Oral Reading Recognition. The oral reading recognition test is a test in which participants are asked to read and pronounce words as accurately as possible. Pronunciation is judged by the test administrator and a score is given to each response (minimum = 0, maximum = 25). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery Pattern Comparison Test Score	2, 4, and 6 months post op	The NIH Toolbox Cognition Battery evaluates cognitive function with Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Picture Vocabulary Test, Pattern Comparison Processing Speed Test, Picture Sequence Memory Test, and Oral Reading Recognition. The pattern comparison test is a test in which participants are presented with two pictures and are asked to discern whether they are he same or different. Correct answers are given one point for up to a maximum of 130 trials (minimum = 0, maximum = 130). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery Picture Sequencing Test Score	2, 4, and 6 months post op	The picture sequencing test is a test of episodic memory in which participants are asked to recall increasingly lengthy series of illustrated objects and activities that are presented in a particular order on a computer screen. Participants are given credit for each adjacent pair of pictures they correctly place up to the maximum value for the sequence, which is one less than the sequence length (minimum = 0, maximum = 105). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in NIH Toolbox Cognition Battery Picture Vocabulary Test Score	2, 4, and 6 months post op	The NIH Toolbox Cognition Battery evaluates cognitive function with Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test, Picture Vocabulary Test, Pattern Comparison Processing Speed Test, Picture Sequence Memory Test, and Oral Reading Recognition. The picture vocabulary test is a test in which participants are presented with an audio recording of a word and four photographic images on the computer screen and asked to select the picture that most closely matches the meaning of the word (minimum = 0, maximum = 25). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Neuro-QOL Scale v1.0 Communication Short Form	2, 4, and 6 months post op	The Neuro-QOL Scale v1.0 Communication short form evaluates one's difficulty with communication. Participants respond to questions on a 1-5 scale (minimum = 5, maximum = 25). Higher scores indicate better function. A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.
Change From Preoperative Baseline in the Beck Anxiety Inventory (BAI)	2, 4, and 6 months post op	The Beck Anxiety Inventory is a 21 question self-report inventory which evaluates a person's severity of anxiety. Items are answered on a 0 - 3 scale. Higher values indicate worse function (possible min score = 0, possible max score = 63). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Study Participants Aggregate baseline data for all study participants	31
Total	31

Baseline characteristics

Characteristic	All Study Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	5 Participants
Age, Categorical Between 18 and 65 years	26 Participants
Age, Continuous	58.85 years STANDARD_DEVIATION 7.6
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	1 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	28 Participants
Region of Enrollment United States	31 participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 30	0 / 30
other Total, other adverse events	2 / 31	0 / 31	0 / 31
serious Total, serious adverse events	3 / 31	4 / 31	0 / 31

Outcome results

Primary

Change From Preoperative Baseline in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS Part III) Off Medications

A blinded examiner will measure Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 motor scores off medications. MDS-UPDRS Part III is a motor examination consisting of 18 summed items where the investigator rates the severity of Parkinson's motor symptoms based on a scale of 0 - 4. Higher values indicate worse function (possible min score = 0, possible max score = 72). A change between baseline and performance at 2, 4, and 6 months post surgery is reported here. Score calculation is baseline - performance while on directional DBS guided by behavior, baseline - performance while on omnidirectional DBS guided by behavior, and baseline - performance while on directional DBS guided by biomarkers.

Time frame: 2, 4, and 6 months post op