Clinical trial NCT02401308: Trial Comparing Functional Outcomes of Awake vs. Asleep Deep Brain Stimulation (DBS) for Parkinson's Disease
Official title: Randomized Controlled Clinical Trial Comparing Functional Outcomes of Awake vs. Asleep Deep Brain Stimulation (DBS) for Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Parkinson's Disease
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
First posted: 2015-03-27
Enrollment: 1
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Functional Outcomes
timeFrame: 6 months post-operatively
Secondary outcomes:
measure: Neurocognitive Function
timeFrame: 6 months post-operatively
measure: Quality of Life
timeFrame: 6 months post-operatively
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute / St. Joseph's Hospital & Medical Center
state: Arizona
Study officials:
affiliation: Barrow Neurological Institute / St. Joseph's Hosptial and Medical Center
name: Francisco A Ponce, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ostrem JL, Galifianakis NB, Markun LC, Grace JK, Martin AJ, Starr PA, Larson PS. Clinical outcomes of PD patients having bilateral STN DBS using high-field interventional MR-imaging for lead placement. Clin Neurol Neurosurg. 2013 Jun;115(6):708-12. doi: 10.1016/j.clineuro.2012.08.019. Epub 2012 Sep 1.
citation: Nakajima T, Zrinzo L, Foltynie T, Olmos IA, Taylor C, Hariz MI, Limousin P. MRI-guided subthalamic nucleus deep brain stimulation without microelectrode recording: can we dispense with surgery under local anaesthesia? Stereotact Funct Neurosurg. 2011;89(5):318-25. doi: 10.1159/000330379. Epub 2011 Sep 15.
citation: Harries AM, Kausar J, Roberts SA, Mocroft AP, Hodson JA, Pall HS, Mitchell RD. Deep brain stimulation of the subthalamic nucleus for advanced Parkinson disease using general anesthesia: long-term results. J Neurosurg. 2012 Jan;116(1):107-13. doi: 10.3171/2011.7.JNS11319. Epub 2011 Oct 14.
citation: Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk J, Huang GD; CSP 468 Study Group. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009 Jan 7;301(1):63-73. doi: 10.1001/jama.2008.929.
citation: Pezeshkian P, DeSalles AA, Gorgulho A, Behnke E, McArthur D, Bari A. Accuracy of frame-based stereotactic magnetic resonance imaging vs frame-based stereotactic head computed tomography fused with recent magnetic resonance imaging for postimplantation deep brain stimulator lead localization. Neurosurgery. 2011 Dec;69(6):1299-306. doi: 10.1227/NEU.0b013e31822b7069.
citation: Papanastassiou V, Rowe J, Scott R, Silburn P, Davies L, Aziz T. Use of the Radionics Image Fusiontrade mark and Stereoplantrade mark programs for target localization in functional neurosurgery. J Clin Neurosci. 1998 Jan;5(1):28-32. doi: 10.1016/s0967-5868(98)90197-7.
citation: Alexander E 3rd, Kooy HM, van Herk M, Schwartz M, Barnes PD, Tarbell N, Mulkern RV, Holupka EJ, Loeffler JS. Magnetic resonance image-directed stereotactic neurosurgery: use of image fusion with computerized tomography to enhance spatial accuracy. J Neurosurg. 1995 Aug;83(2):271-6. doi: 10.3171/jns.1995.83.2.0271.
citation: Kooy HM, van Herk M, Barnes PD, Alexander E 3rd, Dunbar SF, Tarbell NJ, Mulkern RV, Holupka EJ, Loeffler JS. Image fusion for stereotactic radiotherapy and radiosurgery treatment planning. Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1229-34. doi: 10.1016/0360-3016(94)90499-5.