Deep Brain Stimulation of the Cuneiform Nucleus for Levodopa-resistant Freezing of Gait in Parkinson's Disease

Study Overview
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Brief Summary
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The purpose of this research study is to determine if DBS is a safe and effective therapy for severe freezing of gait in patients with Parkinson's Disease. Freezing of gait (FOG) is a particularly debilitating motor deficit seen in a subset of patients with Parkinson's Disease (PD).

Official Title
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Deep Brain Stimulation of the Cuneiform Nucleus for Levodopa-resistant Freezing of Gait in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Vercise DBS System


Participation Criteria
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Eligibility Criteria
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Inclusion: Confirmed Parkinson's Disease according to movement disorder neurologist with documented exclusion of other disorders such as fronto-temporal dementia (FTD)/ frontal gait disorder/normal pressure hydrocephalus (NPH)/progressive supranuclear palsy (PSP) PD stage3 ON medication, with severe gait dysfunction and predominant axial symptoms: Movement Disorder Society-Unified Parkinson's Disease Rating Scale Tremor Dominant (MDS-UPDRS TD), Postural Instability Gait Difficulty (PIGD) ratio ≤ 0.90 and Freezing Of Gait Questionnaire (FOGQ) score > 12. Age 40-75 with good response to Levodopa (defined as greater than 20% improvement in UPDRS score) FOG refractory to LEVODOPA>600 mg 6. Minimal tremor, bradykinesia, and rigidity symptoms, or well controlled with Levodopa and/or with already implanted STN/GPi DBS. a) Poor candidate for STN or GPi DBS due to good control of tremor, bradykinesia, and rigidity symptoms with Levodopa b) or Post-operative STN/GPi DBS PD patients with significant residual non-levodopa responsive postural and gait instability Must agree to full 6-month participation in study. Exclusion: Individuals with major executive dysfunction Individuals with dementia, as defined by the Mattis Dementia Rating Scale-2 (DRS-2) score ≤ 130 Individuals with other neurocognitive impairments Individuals who have depression, as defined for example by the Beck Depression Inventory II (BDI-II) > 25 Presence of major medical co-morbidities and other surgical contra-indications such as coagulopathy Individuals who require diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT) Individuals with a history of prior intracranial surgery Individuals with a metallic implant in their head that is not MRI compatible (e.g., aneurysm clip, cochlear implant) Individuals with active implantable devices anywhere in the body (e.g. cardiac pacemaker, defibrillator, spinal cord stimulator, implanted medication pump) Individuals who are pregnancy or desire to become pregnant during the study Individuals who are breastfeeding12. Individuals who are on investigational drugs and any other intervention (not part of the guidelines for management of Parkinson's Disease) known to have a potential impact on outcome Subjects utilizing recreational drugs at the time of screening will be excluded from the study with the exception of medicinal marijuana

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vercise DBS Group<br>All participants will have the Vercise DBS system implanted. | Device: Vercise DBS System<br>* Vercise Deep Brain Stimulation (DBS) System that consists of two bilateral directional DBS Cartesia electrodes implanted in the cuneiform nucleus and a Gevia generator implanted in the upper chest area just below the clavicle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Gait Velocity | Percent change in gait velocity with and without bilateral cuneiform nucleus deep brain stimulation. Over a distance of 3 meters, gait velocity will be measured using the timed Up and Go test instrumented with Mobility Lab accelerometers. | Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op | 
| Percent change in UPDRS Part III on/off stimulation | Percent change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III on/off stimulation across study visits relative to pre-operative assessment | Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in FOG Questionnaire | Freezing of Gait (FOG) Questionnaire is a 6-item questionnaire with each item scored from 0-4. The total score ranges from 0-24 with the higher score indicating more severe freezing of gait . | Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op | 
| Percent Change in PDQ 39 | Parkinson's Disease Questionnaire (PDQ-39) is 39-item questionnaire with a total score ranging from 0-156 with the higher score indicating poorer quality of life. | Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op | 
| Percent Change in PDQ-L | Parkinson's Disease Quality of Life Questionnaire is a 37-item questionnaire with a total score ranging from 0-185 with the higher score indicating poorer quality of life. | Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op | 
| Percent Change in Muscle Amplitude | Percent change in muscle amplitude during gait testing using electromyography (EMG) | Baseline, 24 weeks | 
| Percent Change in number of Falls | Percent change in number of falls during gait testing sessions and on item 13 of UPDRS III (falls unrelated to freezing) | Baseline, 24 weeks |