Subthalamic Steering for Therapy Optimization in Parkinson's Disease

Study Overview
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Brief Summary
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Twenty patients with idiopathic Parkinson's disease (PD) will be included into this single center randomized controlled double-blind clinical trial (RCT) in a cross-over design. The treatment consists of two different stimulation settings using (i) conventional omnidirectional stimulation of the subthalamic nucleus [STN_O] as active comparator and (ii) directional steering of STN stimulation via a segmented electrode contact [STN_D].

Detailed Description
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Twenty PD patients will be enrolled in this cross-over double-blind RCT to evaluate both the safety and efficacy of directional STN stimulation [STN_D] compared with standard omnidirectional STN stimulation [STN_O]. The primary outcome measure is objectively quantified muscle rigidity of the upper extremity, i.e., surface EMG recordings of the biceps and triceps muscle during standardized extension/flexion of the elbow joint (Levin et al., 2009) assessed 6 months after implantation in cross-over design. The trial is designed to detect with an 80% power a change of 0.27 mA of the therapeutic stimulation threshold with two-tailed P < 0.05 (Wilcoxon rank sum test). Secondary outcome measures address clinical motor, non-motor, neurocognitive and neuropsychiatric symptoms, freezing of gait, and quality of life. Visits are scheduled at weeks 1 (V1), 6 (V2), 24 (V3), 27 (V4), and 30 (V5) from baseline (V0).

Official Title
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Subthalamic Steering for Therapy Optimization in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Omnidirectional Deep Brain Stimulation of STN
* Device: Directional Deep Brain Stimulation of STN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Idiopathic Parkinson's disease (according to the British Brain Bank criteria (Hughes, 1992) including genetic forms Exclusion Criteria: Cognitive impairment (Mini Mental State Exam < 20) Suicidality, Psychosis Other severe pathological chronic condition that might confound treatment effects or interpretation of the data Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: STN_O<br>Omnidirectional Deep Brain Stimulation of STN | Device: Omnidirectional Deep Brain Stimulation of STN<br>* Deep Brain Stimulation<br>|
| Experimental: STN_D<br>Directional Deep Brain Stimulation of STN | Device: Directional Deep Brain Stimulation of STN<br>* Deep Brain Stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Rigidity | Surface-Electromyography (EMG) of M. biceps brachii and M. triceps brachii | 6 months post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical motor and non-motor symptoms (1) | MDS-UPDRS I | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (2) | MDS-UPDRS II | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (3) | MDS-UPDRS III | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (4) | MDS-UPDRS IV | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (5) | Bradykinesia evaluation | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (6) | Tremor evaluation | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (7) | Deep brain stimulation impairment scale (DBS-IS): the scale consists of 22 questions and 6 subscales; subscales: 1. postural instability and gait difficulties (range 0-20), 2. cognitive impaiment (range 0-20), 3. speaking problems (range 0-12), 4. apathy (range 0-12), 5. impulsivity (range 0-12), and 6. difficulties related to DBS device (range 0-12); Ʃ 1-6 DBS-IS total range: 0-88; Ʃ 1-5 DBS-IS total range: 0-76; higher values represent worsening of symptoms | 6 months post-operatively | 
| Clinical motor and non-motor symptoms (8) | Clinical global impression self | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (1) | Modulation range | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (2) | Spatial with a visual Odd-Ball test | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (3) | Verbal Working Memory with an auditory Odd-Ball test | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (4) | Power of Attention (Cognitive Drug Research Battery) | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (5) | Digit Vigilance Accuracy (Cognitive Drug Research Battery) | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (6) | Executive functions with One Touch Tower of London (Cambridge Neuropsychological Test Automated Battery, CANTAB) | 6 months post-operatively | 
| Neurocognitive and non-motor symptoms (7) | Montreal Cognitive Assessment (MoCA) | 6 months post-operatively | 
| Neuropsychiatric symptoms (1) | Beck Depression Inventory (BDI) | 6 months post-operatively | 
| Neuropsychiatric symptoms (2) | Apathy Scale/Lille Apathy rating scale/Neuropsychiatric inventory | 6 months post-operatively | 
| Freezing of gait (1) | Capsit-PD | 6 months post-operatively | 
| Freezing of gait (2) | Freezing of Gait Assessment Course | 6 months post-operatively | 
| Quality of life | Parkinson's Disease Questionaire (PDQ-39) | 6 months post-operatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STN, DBS, steering, segmented electrode leads