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

Not Applicable

Terminated

Conditions: Parkinson's Disease

Interventions: Procedure: Deep Brain Stimulation surgery

Registration Number: NCT02401308

Lead Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Awake DBS Surgery	Deep Brain Stimulation surgery	Deep brain stimulation surgery: Parkinson's patients undergoing traditional "awake" DBS surgery utilizing microelectrode recordings and intra-operative stimulation
Asleep DBS Surgery	Deep Brain Stimulation surgery	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.

Primary Outcome Measures

Name	Time	Method
Functional Outcomes	6 months post-operatively	Motor function outcomes using accepted metrics for Parkinson's disease - the Unified Parkinson's Disease Rating Scale \[UPDRS\] obtained in 3 states: 1. medication "off" / device "on". 2. Medication "off" / device "off" 3. medication "on" / device "on"

Secondary Outcome Measures

Name	Time	Method
Quality of Life	6 months post-operatively	Parkinson's Disease Questionnaire-39 to evaluate the patient's assessment of their quality of life following DBS surgery
Neurocognitive Function	6 months post-operatively	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.