The Effectiveness of Alternating Stimulation in Preventing Tolerance in Essential Tremor Patients

Study Overview
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Brief Summary
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The purpose of this study is to investigate the hypothesis that alternating DBS parameters on a weekly basis will prevent tolerance to stimulation and thus waning of benefit, compared with non-alternating stimulation. The primary endpoint will be preserved tremor control with the alternating group compared with standard treatment using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS). Key secondary endpoints will be preserved activities of daily living measures as well as preserved tremor control as quantified by motion sensor data. This study has one primary aim: To determine if alternating DBS stimulation parameters on a weekly basis will be superior at preserving tremor control compared with usual stimulation (non-alternating stimulation) in ET patients with VIM DBS.

Official Title
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The Effectiveness of Alternating Ventral Intermediate Nucleus Deep Brain Stimulation Parameters in Preventing Tolerance in Essential Tremor Patients

Conditions
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Essential Tremor, Deep Brain Stimulation

Intervention / Treatment
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* Other: Alternating stimulation
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinically diagnosed ET who have had placement of VIM DBS and are willing to undergo a baseline programming visit and 12-week follow-up assessment At least initial benefit from VIM DBS as judged by patient report and clinician exam VIM DBS placement no less than three months from entry into study Patients must demonstrate ability to use patient programmer to switch between group settings on a weekly basis Ability to wear wrist monitor for 2 week intervals, twice during the study 6. Patients with the following IPG types: Activa PC, SC or RC Exclusion Criteria: Atypical tremor disorder including but not limited to tremor due to multiple sclerosis, medication-induced tremor, Parkinson's disease or parkinsonian syndrome DBS placement complicated by infection, hemorrhage or stroke Previous thalamotomy (either stereotactic, gamma knife or focused ultrasound) or previous DBS surgery resulting in explantation and reimplantation Known incorrect or poor lead placement Inability to change group settings on a weekly basis at least 75% of the time Inability to tolerate 12-week period without additional programming changes, including voltage stimulation adjustment Inability to tolerate 12-week period without adjustment of anti-tremor medications, including primidone, beta-blockers, gabapentin, topiramate and/or benzodiazepines Battery voltage < or equal to 2.70V Patient with the following IPG types: Soletra, Kinetra or Itrel Inability to tolerate two group settings due to side effects or lack of efficacy

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>In the placebo cohort, subjects will alternate their DBS parameters between group A and group B every week for 12 weeks, but they will be blinded to the fact that their group A and group B are equivalent. | Other: Placebo<br>* The control cohort will receive Setting A but Setting B will be identical to Setting A.<br>|
| Active Comparator: Treatment<br>In the treatment cohort, subjects will alternate their DBS parameters between group A and group B every week for 12 weeks. | Other: Alternating stimulation<br>* Two different, but equally efficacious, settings will be determined for each subject. The settings will differ by a minimum of two of the following parameters: electrode configuration, voltage, frequency and pulse width. The different settings will be named Setting A and Setting B. The treatment cohort will receive both Setting A and Setting B that will differ by the parameters listed above.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) performance sub scale at 12 weeks |  | Through study completion, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TETRAS ADLs scale at 12 weeks |  | Through study completion, at 12 weeks | 
| Motion sensor data to detect tremor | Patients will wear motion sensor device to detect tremor characteristics | Two weeks after initial visit; and again at weeks 10-12 |