Clinical trial NCT03353688: Biomarkers to Guide Directional DBS for Parkinson's Disease
Official title: Noninvasive Biomarkers to Advance Emerging DBS Electrode Technologies in Parkinson's Disease (SUNDIAL, SUbthalamic Nucleus DIrectionAL vs Circular Stimulation Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Keywords: Parkinson's
Parkinson Disease
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2017-11-27
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Preoperative Baseline in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part 3 (MDS-UPDRS Part III) "Off" Medications
timeFrame: 2, 4, and 6 months post op
measure: Treatment Preference Survey Programming Strategy Preference
timeFrame: 4 months post surgery
Secondary outcomes:
measure: Change From Preoperative Baseline in the Beck Depression Inventory-2 (BDI-2)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Beck Anxiety Inventory (BAI)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Delayed Recall Raw Score (Versions AB, CD, CR, GE)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Recognition Raw Score (Versions AB, CD, CR, GE)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Auditory Verbal Learning Test (AVLT) Learning Raw Score (Versions AB, CD, CR, GE)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Letter Fluency Test Raw Score (Version: CFL, FAS)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Voice Handicap Index
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Communicative Participation Item Bank (CPIB)
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the 9-Hole Pegboard Test
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Gait Initiation Test
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Stepping Thresholds Test
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Quiet Stance Measure
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Parkinson's Disease Quality of Life
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the the Neuro-QOL Item Bank v1.0 "Positive Affect and Well-Being" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.1 "Satisfaction With Social Roles and Activities" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Item Bank v2.0 "Cognitive Function" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 "Lower Extremity Function (Mobility)" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 "Upper Extremity Function (Fine Motor, ADL)" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 "Stigma" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Scale v1.0 "Communication" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Neuro-QOL Item Bank v1.0 "Emotional and Behavioral Dyscontrol" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 "Global Health" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 "Global Health Mental Health Score"
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v2.0 "Ability to Participate in Social Roles and Activities" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 "Emotional Distress - Anxiety" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 "Emotional Distress - Depression" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 "Fatigue" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v2.0 "Physical Function" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in Patient-Reported Outcomes Measurement Information System PROMIS v1.0 "Sleep Disturbance" Short Form
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery Dimensional Change Card Sort Score
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery Flanker Test Score
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery List Sorting Working Memory Test Score
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery Oral Reading Test Score
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery Pattern Comparison Test Score
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery Picture Sequencing Test Score
timeFrame: 2, 4, and 6 months post op
measure: Change From Preoperative Baseline in NIH Toolbox Cognition Battery Picture Vocabulary Test Score
timeFrame: 2, 4, and 6 months post op
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Harrison Walker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Black SD, Del Bene VA, Celka AS, Guthrie B, Martin RC, Olson J, Shumake J, Walker HC. Nascent visual artistic expression following right hemisphere subthalamic nucleus deep brain stimulation for Parkinson's disease. Parkinsonism Relat Disord. 2022 Jun;99:47-50. doi: 10.1016/j.parkreldis.2022.04.020. Epub 2022 May 1. No abstract available.