Variable Frequency Stimulation of Subthalamic Nucleus for Freezing of Gait in Parkinson's Disease

Study Overview
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Brief Summary
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This is the first study on the effect of the variable frequency stimulation (VFS) on Freezing of gait (FOG) in Parkinson's disease (PD) patients with STN DBS. FOG has responded poorly to High frequency stimulation (HFS) but can be alleviated by relatively VFS. This study would have significant clinical implications in the management of Freezing of gait (FOG) in these PD patients with subthalamic nucleus (STN) DBS. The investigators hypothesize that VFS could have better effect on FOG than HFS and low frequency stimulation (LFS).

Detailed Description
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HFS of STN provides consistent, long-term improvement of the cardinal motor signs of PD, such as bradykinesia, tremor and rigidity. FOG has responded poorly to HFS and tends to continue to deteriorate over time, but this can be alleviated by relatively LFS. Evidence has indicated that LFS-STN can improve axial signs in some but not all PD patients, but most of them experienced loss of efficacy in the short term. Then comes to the little improvement or even worse of tremor, rigidity and bradykinesia, which consists of the three main symptoms of Parkinson's disease. Thus even if axial problems could be solved by LFS in a long way, it could also be hard to tolerate by those patients. The effect of VFS on FOG will be studied. The investigators hypothesize that VFS could have better effect on Freezing of gait than HFS and LFS.

Official Title
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Double-Blind Trial of Variable Frequency Stimulation for Freezing of Gait in Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Device: Deep Brain Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were receiving bilateral STN stimulation for more than six months. They were optimized on conventional HFS for control of tremors, rigidity and bradykinesia yet complained of freezing of gait. Subjects had an ability to walk at least 10 meters independently during ON DBS condition. Exclusion criteria: gait disorders perceived by patients as a direct consequence of STN stimulation and not the primary disease. any change in the HFS DBS settings, three months prior to participation in the study. complete inability to walk despite assistance while DBS ON. Subjects responding to reprogramming of chronic DBS settings (report improvement of freezing). Subjects could not tolerate prolonged OFF medication condition.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VFS<br>variable frequency deep brain stimulation (VFS) | Device: Deep Brain Stimulation<br>* Deep Brain Stimulation<br>|
| Active Comparator: HFS<br>high frequency deep brain stimulation (HFS) | Device: Deep Brain Stimulation<br>* Deep Brain Stimulation<br>|
| Active Comparator: LFS<br>low frequency deep brain stimulation (LFS) | Device: Deep Brain Stimulation<br>* Deep Brain Stimulation<br>|
| No Intervention: DBS off<br>deep brain stimulation off | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed Up and Go (TUG) task | variable frequency stimulation (VFS) setting compared to high frequency stimulation (HFS) and low frequency stimulation (LFS) | The outcome of TUG task at 12 months follow-up. | 
| the number of freezing episodes for TUG task | variable frequency stimulation (VFS) setting compared to high frequency stimulation (HFS) and low frequency stimulation (LFS) | The outcome of TUG task at 12 months follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS III scores |  | Outcome of VFS at 6、12 months with reference to baseline HFS | 
| Gait and Falls Questionnaire (GFQ) scores |  | Outcome of VFS at 6、12 months with reference to baseline HFS | 
| the39-item Parkinson's Disease Questionnaire (PDQ-39) scores |  | Outcome of VFS at 6、12 months with reference to baseline HFS | 
| the Freezing of Gait Questionnaire (FOG-Q) scores |  | Outcome of VFS at 6 、12months with reference to baseline HFS | 
| Number of adverse events (AE's) |  | Change from Baseline to 6、12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DBS, VFS, FOG