Unilateral GPi vs Unilateral STN DBS in the Same Patient With PD

Study Overview
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Brief Summary
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The subthalamic nucleus (STN) and globus pallidus interna (GPi) are two main targets in the deep brain stimulation (DBS) treatment for Parkinson's disease (PD). Large randomized controlled trials, in which patients of comparable clinical and demographics were randomized to either GPi DBS or STN DBS, have demonstrated equal effects of both targets in motor symptom improvement, the superiority of STN DBS in the medication reduction and the potential advantage of GPi DBS for cognitive, psychiatric and axial aspects. Unfortunately, in such a highly heterogeneous disease of PD, many of these randomized controlled trials didn't include sufficient subjects and thereby yielded inconsistent results. Moreover, most studies are investigating the difference between GPi and STN in different patients. In order to address the problem, an intra-patient comparison will be made by investigating the acute turning-on effects of unilateral STN stimulation versus unilateral GPi stimulation on axial symptoms, cognition and also cardinal symptoms within each individual patient who received the treatment of combined unilateral STN and contralateral GPi DBS. Axial symptoms including gait, balance and posture, motor symptoms and cognition are comprehensively assessed under two treatment conditions.

Official Title
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Unilateral Pallidal vs Unilateral Subthalamic Nucleus Deep Brain Stimulation in the Same Patient With Parkinson Disease: A Randomized Controlled Trial

Conditions
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Parkinson Disease, Deep Brain Stimulation, Globus Pallidus Interna, Subthalamic Nucleus

Intervention / Treatment
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* Procedure: DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with idiopathic Parkinson's disease Aged between 55 and 75 years, both male and female Patients who have undergone combined unilateral STN and contralateral GPi DBS for more than 6 months A Hoehn-Yahr (H-Y) stage of less than 4 in the off-medication state A left-extremity to right-extremity ratio of less than 0.15 on the Unified Parkinson's Disease Rating Scale part Ⅲ (UPDRS-Ⅲ) in the both off-medication and on-medication states Exclusion Criteria: History of serious psychosis History of intractable epilepsy (i.e., seizures) Diagnosed by the investigators that patients with severe cardiac, liver and kidney diseases, or other serious health conditions Dementia (A Mini-Mental State Examination (MMSE) score of < 24), inability to comprehend the experimental protocol or voluntarily provide informed consent Lack of cooperation Additional reasons for exclusion at the discretion of the clinical investigator Poorly controlled depression or anxiety Past history of suicidal attempt

Ages Eligible for Study
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Minimum Age: 55 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unilateral DBS of the subthalamic nucleus (STN)<br>To deliver unilateral STN DBS, bilateral stimulation will be turned off for three hours, and then turn on the unilateral STN DBS. The STN stimulation will be programmed as previous parameter configuration with optimal therapeutic benefits. Participants will be asked to complete a comprehensive set of assessments under unilateral STN stimulation in the off-medication state. 45 minutes after taking regular medication, participants need to complete the second set of assessments in the on-medication state. | Procedure: DBS<br>* Unilateral DBS for treatment of patients with PD<br>|
| Experimental: Unilateral DBS of the globus pallidus interna (GPi)<br>To deliver unilateral GPi DBS, bilateral stimulation will be turned off for three hours, and then turn on the unilateral GPi DBS. The study protocol is identical to the intervention of unilateral STN DBS but it was done on a different day. | Procedure: DBS<br>* Unilateral DBS for treatment of patients with PD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Timed Up-and-Go (TUG) task scores between treatment conditions in the on- and off- medication states | Timed Up-and-Go task is a well-defined objective gait measurement. The task requires an individual to stand up, walk 5 m, turn, walk back, and sit down. The time taken to complete the test is strongly correlated with the level of functional mobility. This test will be videotaped and scored by two blinded neurologists. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in total Uniﬁed Parkinson's Disease Rating Scale Part Ⅲ (UPDRS Ⅲ) scores between two treatment conditions in the on- and off- medication states | Uniﬁed Parkinson's Disease Rating Scale Part Ⅲ measures the motor severity of Parkinson's disease. UPDRS Ⅲ score has a range of 0 (no symptoms) to 132 (severe disease symptoms). | 6 months | 
| Differences in Burg Balance Scale (BBS) scores between two treatment conditions in the on- and off- medication states. | Burg Balance Scale measures patients' static and dynamic balance abilities. BBS score has a range of 0 (severe balance problems) to 56 (no balance problems). | 6 months | 
| Differences in postural angles between two treatment conditions in the on- and off- medication states. | The measurement of postural angles is the same as the paper (Yamada et al) published in J Neurol Neurosurg Psychiatry | 6 months | 
| Differences in Water Swallow Test (WST) scores between treatment conditions in the on- and off- medication states. | The Water Swallow Test is frequently used in clinical practice as a functional assessment to detect dysphagia, with stage 1 indicating severe dysphagia and stage 6 indicating normal swallowing function. | 6 months | 
| Differences in Swallowing Disturbance Questionnaire (SDQ) scores between treatment conditions in the on- and off- medication states. | The Swallowing Disturbance Questionnaire is created as a self-rated dysphagia screening tool in PD, with a range of 0 (normal swallowing function) to 42 (severe dysphagia). | 6 months | 
| Differences in voice parameters between treatment conditions in the on- and off- medication states. | Voice recording at a sampling rate of 44.1 kHz using 16-bit quantification will be conducted in a sound-treated room using a microphone and a digital voice recorder with a mouth-to-microphone distance of 15 cm. The recorded voices will then be used for a composit acoustic analysis. | 6 months | 
| Differences in Voice Handicap Index (VHI) between treatment conditions in the on- and off- medication states. | The Voice Handicap Index is a self-administered instrument, comprising 30 items on voice-related dysfunction. VHI has a range of 0 (normal voice function) to 120 (severe voice dysfunction). | 6 months |