Clinical trial NCT02418858: Functional Outcomes of Awake vs. Asleep Deep Brain Stimulation (DBS) for Essential Tremor
Official title: Randomized Controlled Clinical Trial Comparing Functional Outcomes of Awake vs. Asleep Deep Brain Stimulation (DBS) for Essential Tremor
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Essential Tremor
Keywords: Essential tremor
DBS
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
First posted: 2015-04-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 and intra-operative test stimulation. 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 awake during the procedure.

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. Essential tremor (ET) patients undergo intra-operative test stimulation to refine the lead location and ensure the absence of sustained side effects. This 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 provokes significant anxiety and fear in some patients.

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 and intra-operative test stimulation. 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 awake during the procedure.

If asleep DBS produces clinical results equivalent to awake DBS surgery, the possible advantages include shorter surgical time, improved patient comfort, better access to DBS for patients, and cost savings for the hospital.

To date (August 2011 - September 2014), 157 patients have undergone asleep DBS surgery and 141 patients have undergone traditional awake DBS surgery. ET patients constitute 76 of the total surgeries - 50 patients underwent awake surgery and 26 underwent asleep 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 for patients with the diagnosis of Essential tremor. 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 three month functional outcomes using accepted outcome metrics for ET, including an objective tremor rating scale (Fahn-Tolosa-Marin Tremor Rating Scale), a tremor Activities of Daily Living (ADL) questionnaire (Bain and Findley Tremor ADL scale), and a tremor quality of life questionnaire : Quality of Life in Essential Tremor Questionnaire \[QUEST\]). Parkinson Meter and Life Pulse tremor readings (two iPhone accelerometer applications) will also be collected. . 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, 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 null hypothesis is that asleep DBS results in inferior tremor ratings 3-months after surgery when compared to awake DBS. Our secondary aim will be to evaluate any cognitive changes associated with DBS surgery selection (awake vs. asleep) in ET 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.

Eligibility criteria: Inclusion Criteria:

* Essential Tremor diagnosed by criteria listed in the Consensus statement of the Movement Disorders Society on Tremor
* 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 Essential Tremor
* 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

Primary outcomes:
measure: Functional Outcomes
timeFrame: 12 weeks post-operatively
measure: Quality of Life Assessment
timeFrame: 12 week post-operatively
Secondary outcomes:
measure: Neurocognitive Function
timeFrame: 6 months post-operatively
Other outcomes:
measure: Tremor Reduction
timeFrame: 12 weeks post-operatively
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute / St. Joseph's Hospital and Medical Center
state: Arizona
Study officials:
affiliation: Barrow Neurological Institute / St. Joseph's Hospital and Medical Center
name: Francisco A Ponce, MD
role: PRINCIPAL_INVESTIGATOR
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