Phase 1 study evaluating the safety of combined bilateral globus pallidus internus (GPi) and nucleus basalis of Meynert (NBM) stimulation in treating levodopa responsive motor symptoms of Parkinsonism and cognitive dysfunction, respectively, in patients with moderate to advanced Parkinson's disease having mild cognitive impairment.
This study aims to provide a proof of safety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients with moderate to advanced Parkinson's disease having mild cognitive impairment. GPi stimulation with high-frequency ameliorates the cardinal motor symptoms and motor complications in Parkinson's disease patients, and this present study also wants to determine if additional NBM stimulation, with low-frequency stimulation, improves or slows progression of cognitive decline in patients with moderate to advanced Parkinson's disease having mild cognitive impairment, and to evaluate the effect of NBM stimulation on gait and balance impairment. Study Design: Prospective single center Phase 1 study with double-blind randomized delayed activation of basal nucleus of Meynert neurostimulation (staggered onset design). Planned Number of Subjects: 10 patients. Planned Number of Sites / Countries: Single center in Brazil. Study schedule: * Presurgical baseline evaluation (motor on and off medication state; cognitive testing in best motor on state). * DBS Implant Procedure. * Postsurgical baseline evaluation (motor off state; cognitive testing in best motor on state) at 3±1 weeks after surgery and activation of globus pallidus internus neurostimulation using individualized stimulation parameters after a standard monopolar review. * Regular adjustments of the GPi stimulation parameters aiming at the best motor improvement. * Visit 1 (16 weeks after activation of GPi neurostimulation): motor off medication + GPi stimulation state, cognitive testing in on medication + GPi stimulation state. Randomization and blinded activation of NBM neurostimulation according to a 1:1 scheme. * Visit 2 (16 weeks after randomization): motor off and on medication + stimulation state (GPi stimulation ± NBM stimulation); cognitive testing in motor on medication + stimulation state (GPi stimulation ± NBM stimulation). Activation of NBM neurostimulation in all patients. * Visit 3 (16 weeks after activation of NBM stimulation in all patients): motor off and on medication + GPi and NBM stimulation state; cognitive testing in motor on medication + GPi and NBM stimulation state. * Annual follow-up visit for up to 5 years after activation of NBM stimulation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
10
Deep brain stimulation implantation of a Vercise neurostimulation system in GPi and NBM, at the same trajectory.
Bilateral high-frequency neurostimulation of the GPi using a Vercise neurostimulation system
Bilateral low-frequency neurostimulation of the NBM using a Vercise neurostimulation system
University of São Paulo General Hospital
São Paulo, Brazil
RECRUITINGSafety of combined bilateral Globus Pallidus internus (GPi) and Nucleus Basalis of Meynert (NBM) stimulation in patients with moderate to advanced Parkinson's disease with mild cognitive impairment as determined by reported adverse events.
Safety of combined bilateral GPi and NBM stimulation in patients with moderate to advanced Parkinson's disease having mild cognitive impairment as determined by reported adverse events.
Time frame: 36 weeks
Change in Parkinson's Disease - Cognitive Rating Scale (PD-CRS).
This scale can range from 0 to 134, and higher scores mean a better outcome.
Time frame: 36 weeks
Change in Mattis Dementia Rating Scale.
This scale can range from 0 to 144, and higher scores mean a better outcome.
Time frame: 36 weeks
Change in Verbal Fluency Battery.
FAS and animals
Time frame: 36 weeks
Change in Trail Making Task.
Trail Making Task Part A + B.
Time frame: 36 weeks
Change in Stroop Test.
Stroop Test (Victoria Version).
Time frame: 36 weeks
Change in Symbol Digit Modalities Test.
Digit symbol coding - WAIS.
Time frame: 36 weeks
Change in Parkinson's Disease Questionnaire for quality of life (PDQ-39).
This questionnaire can range from 0 to 100%, and higher scores mean a worse outcome.
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Ineffective neurostimulation by setting 0mA output at the Vercise neurostimulation system
Time frame: 36 weeks
Change in Questionnaire of the EuroQol-group (EQ-5D-5L).
This questionnaire can range from 0 to 25, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Unified Parkinson's Disease Rating Scale section I (UPDRS I).
This scale can range from 0 to 52, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Unified Parkinson's Disease Rating Scale section II (UPDRS II).
This scale can range from 0 to 52, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Unified Parkinson's Disease Rating Scale section III (UPDRS III).
This scale can range from 0 to 132, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Unified Parkinson's Disease Rating Scale section IV (UPDRS IV).
This scale can range from 0 to 24, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess step speed.
Time frame: 36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess number of steps per minute.
Time frame: 36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess distance between heels.
Time frame: 36 weeks
Change in objective assessment of gait measured by a sensor (MobilityLab) that assess balance.
Time frame: 36 weeks
Change in objective assessment of gait measured by Time Up and Go - Test 3 meters (TUG test 3M).
Time frame: 36 weeks
Change in objective assessment of gait measured by Time Up and Go dual task - Test 3 meters (TUG dual task - test 3M).
Time frame: 36 weeks
Change in objective assessment of gait measured by freezing of gait score (FOG score).
Time frame: 36 weeks
Change in New Freezing of Gait Questionnaire (N-FOG).
This questionnaire can range from 0 to 28, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Falls Efficacy Scale International (FES-I).
This questionnaire can range from 0 to 64, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Activities-Specific Balance Confidence Scale (ABC scale).
This scale can range from 0 to 100%, and higher scores mean a better outcome.
Time frame: 36 weeks
Change in Beck Depression Inventory (BDI).
This inventory can range from 0 to 63, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Beck Anxiety Inventory (BAI).
This inventory can range from 0 to 63, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Starkstein Apathy Scale.
This scale can range from 0 to 42, and higher scores mean a worse outcome.
Time frame: 36 weeks
Change in Neuropsychiatric Inventory (NPI).
Time frame: 36 weeks
Change in Ardouin Scale of Behavior in Parkinson's Disease.
This scale can range from 0 to 84, and higher scores mean a worse outcome.
Time frame: 36 weeks