Trial Comparing Functional Outcomes of Awake vs. Asleep Deep Brain Stimulation (DBS) for Parkinson's Disease

Study Overview
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Brief Summary
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The purpose of the proposed study is to demonstrate that the functional outcomes of DBS surgery utilizing the asleep technique are not inferior to those reported for traditional awake DBS technique.

Detailed Description
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Traditional DBS is performed without general anesthesia with the patient awake. Local anesthetic is used to numb the skin and tissue where the incision is made, and the patients are given mild sedatives to alleviate anxiety and discomfort. Parkinson's patients need to be off their medications during awake DBS in order to obtain single-unit cellular recordings to locate and map the desired target. The process of electrophysiological mapping can result in multiple brain penetrations during lead placement, and the entire procedure may last anywhere from 4-6 hours on average. The concept of being awake during brain surgery and being off medications are significant concerns for some patients. In addition, it is widely recognized that microelectrode recording increases the risk of hemorrhage during DBS surgery. Recently, there has been increasing interest in performing DBS under general anesthesia, where the stimulated targets are located anatomically (i.e. on MRI) rather than physiologically via microelectrode recordings. This technology has been termed asleep DBS and is performed with the patient under general anesthesia. Intraoperative imaging is utilized to verify the stereotactic accuracy of DBS electrodes placement at the time of surgery. Because stereotactic accuracy (and surgical safety) is the surgical endpoint, there is no need for the patient to be off medication and awake during the procedure. Traditional DBS is performed without general anesthesia with the patient awake. Local anesthetic is used to numb the skin and tissue where the incision is made, and the patients are given mild sedatives to alleviate anxiety and discomfort. Parkinson's patients need to be off their medications during awake DBS in order to obtain single-unit cellular recordings to locate and map the desired target. The process of electrophysiological mapping can result in multiple brain penetrations during lead placement, and the entire procedure may last anywhere from 4-6 hours on average. The concept of being awake during brain surgery and being off medications are significant concerns for some patients. In addition, it is widely recognized that microelectrode recording increases the risk of hemorrhage during DBS surgery. The safety and efficacy of the two approaches to DBS surgery have been equivalent, and we are at a position of equipoise with regard to what to offer to patients. To date, there have been no randomized, controlled clinical trials comparing the efficacy and functional outcomes of the two DBS methods. After informed consent is obtained, the patients will undergo routine DBS pre-operative evaluation and diagnostic testing. This includes a pre-operative 3T-MRI with and without gadolinium as well as pre-operative medical clearance by the patient's PCP or general practitioner and/or other medical specialist if necessary. They will also receive a baseline clinical evaluation including both motor function (Unified Parkinson's Disease Rating Scale on and off antiparkinsonian medication) and quality of life (Parkinson's disease Questionnaire-39) if not already completed as part of the routine DBS candidacy evaluation within 2 months of surgery. Patients who elect to participate in this trial will undergo a routine pre-operative neurocognitive evaluation consisting of the following routine evaluative tests: Wechsler Test of Adult Reading, Mattis Dementia Rating Scale 2nd Edition, Wechsler Abbreviate Scale of Intelligence 2nd Edition; Wechsler Memory Scale 3rd edition, Digit Span, Stroop Neuropsychological Screening Test, Trail Making Test, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Animal Naming, Boston Naming Test, Wechsler Memory Scale 4th Edition, Logical Memory, Hopkins Verbal Learning Test - Revised, Brief Visuospatial Memory Test - Revised, Hooper visual Organization Test, Judgment of Line Orientation, Beck Depression Inventory, Beck Anxiety Inventory, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease, Apathy Evaluation Scale; Epworth Sleepiness Scale, The subjects will then be randomized to 2 groups by using random numbers in an envelope system. We anticipate that 120 total patients will need to be enrolled in this pilot study (60 awake, 60 asleep), and thus the numbers 1-120 will be placed in envelopes. An odd number will correspond to the awake DBS procedure, and an even number will indicate an asleep DBS procedure. The purpose of the proposed study is to demonstrate that the functional outcomes of the asleep technique are not inferior to those reported for traditional awake DBS technique. The primary data points for this study will include six month functional outcomes using accepted metrics for Parkinson's disease, including both motor function (Unified Parkinson's Disease Rating Scale [UPDRS] obtained in the medication on and medication off states) and quality of life (Parkinson's Disease Questionnaire-39). The null hypothesis is that asleep DBS results in inferior UPDRS-III scores at 6-months after surgery. Our secondary aim will be to evaluate any cognitive changes associated with DBS surgery selection (awake vs. asleep) in PD patients. Current standard of care for patient selection in DBS focuses primarily on the evaluation of motor symptoms and currently there is no guidance for how a patients' DBS surgery selection (awake vs. asleep) would impact on subsequent neurocognitive function.

Official Title
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Randomized Controlled Clinical Trial Comparing Functional Outcomes of Awake vs. Asleep Deep Brain Stimulation (DBS) for Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Procedure: Deep Brain Stimulation surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's disease per Queens Square criteria Appropriate DBS candidate for multi-disciplinary team consensus Age 18 - 85 years of age Motor skills allowing for capability to complete evaluations Medically cleared for undergoing anesthesia and DBS surgery Exclusion Criteria: Dementia per DSM-V criteria Medical or other condition precluding MRI History of supraspinal CNS disease other than PD Alcohol use of more than 4 drinks per day Pregnancy History of suicide attempt Currently uncontrolled clinically significant depression (BDI>20) History of schizophrenia, delusions, or currently uncontrolled visual hallucinations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Awake DBS Surgery<br>Deep brain stimulation surgery: Parkinson's patients undergoing traditional awake DBS surgery utilizing microelectrode recordings and intra-operative stimulation | Procedure: Deep Brain Stimulation surgery<br>* Deep Brain Stimulation surgery: awake vs. asleep<br>* Other names: DBS;|
| Active Comparator: Asleep DBS Surgery<br>Deep brain stimulation surgery:Parkinson's patients undergoing DBS surgery under general anesthesia utilizing intraoperative imaging to verify the stereotactic accuracy of DBS electrodes placement at the time of surgery. | Procedure: Deep Brain Stimulation surgery<br>* Deep Brain Stimulation surgery: awake vs. asleep<br>* Other names: DBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Outcomes | Motor function outcomes using accepted metrics for Parkinson's disease - the Unified Parkinson's Disease Rating Scale [UPDRS] obtained in 3 states: medication off / device on. Medication off / device off medication on / device on | 6 months post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive Function | Neurocognitive evaluation consisting of the following routine evaluative tests: Wechsler Test of Adult Reading, Mattis Dementia Rating Scale 2nd Edition, Wechsler Abbreviate Scale of Intelligence 2nd Edition; Wechsler Memory Scale 3rd edition, Digit Span, Stroop Neuropsychological Screening Test, Trail Making Test, Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Animal Naming, Boston Naming Test, Wechsler Memory Scale 4th Edition, Logical Memory, Hopkins Verbal Learning Test - Revised, Brief Visuospatial Memory Test - Revised, Hooper visual Organization Test, Judgment of Line Orientation, Beck Depression Inventory, Beck Anxiety Inventory, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease, Apathy Evaluation Scale; Epworth Sleepiness Scale. | 6 months post-operatively | 
| Quality of Life | Parkinson's Disease Questionnaire-39 to evaluate the patient's assessment of their quality of life following DBS surgery | 6 months post-operatively |