Asleep MRI-guided Versus Awake Microelectrode Recording Guided Deep Brain Stimulation in Parkinson's Disease: A Comparative Effectiveness Trial

Study Overview
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Brief Summary
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Rationale: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-accepted treatment for Parkinson's disease (PD). Traditionally, the procedure is performed awake and under local anaesthesia to facilitate intraoperative monitoring via microelectrode recording and test stimulation for exact electrode positioning. Advances in MR imaging allow for clear visualization of the STN and therefore direct targeting. Retrospective series suggest that MRI-guided and image (CT or MRI)-verified STN-DBS under general anaesthesia yields a similar motor outcome and quality of life (QoL) as awake and microelectrode recording-guided surgery with intra-operative clinical testing. MRI-guided and image (CT or MRI)- verified approach potentially has advantages in terms of patient experience and cost-effectiveness. The study proposed here is the first in the world to directly compare both methods. Objective: To compare bilateral MRI-guided and CT-verified STN-DBS under general anaesthesia to awake microelectrode-guided bilateral STN-DBS with intra-operative clinical testing in terms of motor improvement. Study design: A multicentre comparative effectiveness trial with a non-inferiority design. Study population: 158 PD people eligible for bilateral STN-DBS (79 in each arm). Intervention: This study compares two modalities of standard treatment. One arm receives awake microelectrode recording guided bilateral STN-DBS under local anaesthesia with intraoperative clinical testing. The other arm receives MRI-guided and CT-verified bilateral STN-DBS under general anaesthesia. Main study parameters/endpoints: The primary outcome is the change from baseline to one year in Unified Parkinson's Disease Rating Scale part III (UPDRS III) scores (OFF Medication) versus the postoperative scores (OFF medication and ON stimulation). Secondary objectives include patient experience, quality of life, adverse effects and complications, neuropsychological examination, non-motor symptoms (including psychiatric evaluation), reduction in anti-parkinsonian medication, activities of daily living (ADL) functioning and cost- effectiveness.

Official Title
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Asleep MRI-guided and CT-verified Versus Awake Microelectrode Recording Guided Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Comparative Effectiveness Trial

Conditions
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Parkinson Disease

Intervention / Treatment
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* Procedure: bilateral STN deep brain stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 30-75 years of age Idiopathic Parkinson's disease (according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease) Disease duration ≥ 4 years Hoehn & Yahr ≤ 3 (in best ON-medication condition) Despite optimal pharmacological treatment, at least one of the following symptoms: Disturbing response fluctuation Dyskinesia Painful dystonia Drug-resistant tremor ≥30% improvement of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score in a levodopa challenge test, except for tremor dominant PD. This is conform daily clinical practice in all participating centres. Written informed consent Exclusion Criteria: Dementia (Montreal Cognitive Assessment ≤ 25) Previous neurosurgical procedures for PD Structural lesions on brain MRI Contra-indications for DBS surgery Contra-indications for MRI Current depression or history recurrent severe depression History of psychosis Need for nursing care Life expectancy < 2 years

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Awake MER-guided surgical procedure under local anesthesia with intraoperative testing<br>Awake micro-electrode recording-guided surgical procedure under local anesthesia with intraoperative testing | Procedure: bilateral STN deep brain stimulation<br>* bilateral deep brain stimulation of the subthalamic nucleus in people with Parkinson's disease<br>|
| Asleep MRI-guided and CT-verified surgical procedure<br>Asleep MRI-guided and CT-verified surgical procedure | Procedure: bilateral STN deep brain stimulation<br>* bilateral deep brain stimulation of the subthalamic nucleus in people with Parkinson's disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale part III | change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part III (min 0, max. 132; higher score means worse outcome) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reduction in anti-parkinsonian medication | change from baseline to 1 year in levodopa equivalent daily dose (LEDD) | 12 months | 
| health-related quality of life | change from baseline to 1 year in the 39-item Parkinson's Disease Questionnaire (PDQ-39; min. 0, max. 156; higher score means worse outcome) | 12 months | 
| Non-motor aspects of experiences of daily living | change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part I (min. 0, max. 52; higher score means worse outcome) | 12 months | 
| Motor aspects of experiences of daily living measured | change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part II (min. 0, max. 52; higher score means worse outcome) | 12 months | 
| Motor complications after DBS surgery | change from baseline to 1 year in Unified Parkinson's Disease Rating Scale part IV (min. 0, max. 24; higher score means worse outcome) | 12 months | 
| Patient experience and satisfaction | Deep Brain Stimulation Patient Experience Rating Scale (min. 0, max. 224, higher score means better outcome) | during hospitalization and follow up visits at approximately 2 weeks after surgery, 6 and 12 months | 
| Depressive symptoms | change from baseline to 1 year in Beck Depression Inventory-Second Edition (BDI-II; min. 0, max. 63, higher score means worse outcome) | 12 months | 
| Non-Motor Symptoms | change from baseline to 1 year in Non-Motor Symptoms Assessment Scale (NMSS) for Parkinson's disease (min. 0, max. 360, higher score means worse outcome) | 12 months | 
| Impulsivity | change from baseline to 1 year in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP; min. 0, max. 112, higher score means worse outcome) | 12 months | 
| Cognitive impairment | change from baseline to 1 year in Montreal Cognitive Assignment (MoCA; min. 0, max. 30, higher score means better outcome) | 12 months | 
| Anxiety | change from baseline to 1 year in Parkinson Anxiety Scale (PAS, min. 0, max. 12, higher score means worse outcome) | 12 months | 
| Autonomic symptoms | change from baseline to 1 year in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT, min. 0, max. 69, higher score means worse outcome) | 12 months | 
| Neuropsychiatric symptoms | change from baseline to 1 year in he Neuropsychiatric Inventory Questionnaire (NPI-Q, min. 0, max. 36, higher score means worse outcome) | 12 months | 
| Patient's sleepiness | change from baseline to 1 year in the Epworth Sleepiness Scale (ESS; min. 0, max. 24; higher score means worse outcome) | 12 months | 
| Complications and (serious) adverse effects | measured with a standardized check list | 12 months | 
| Cost effectiveness | measured indirectly by duration of operation and duration of hospitalization | during hospitalization (range 3-5 days, median 4 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Brain Stimulation, Parkinson Disease, subthalamic nucleus