Directional Versus Nondirectional DBS for ET

Study Overview
=================
Brief Summary
-----------------
This will be a single center (OHSU) proof of concept trial to demonstrate that directional deep brain stimulation (DBS) creates a larger therapeutic window for the treatment of essential tremor (ET), effectively treats ET, and minimizes effects on speech, gait and balance compared to nondirectional DBS.

Detailed Description
-----------------
Specific Aims: To compare the therapeutic window (TW) of directional versus nondirectional deep brain stimulation for treatment of tremor. Hypothesis: directional DBS will result in a wider TW than nondirectional DBS. To compare the effects of directional versus nondirectional DBS on speech Hypothesis: Objective and subjective speech impairment will occur to a greater extent in nondirectional DBS versus directional DBS optimized for tremor control. To compare the effects of directional versus nondirectional DBS on balance and gait Hypothesis: Objective and subjective balance and gait impairment will occur to a greater extent in nondirectional DBS versus directional DBS optimized for tremor control. To assess efficacy for tremor of nondirectional and directional DBS in an optimized programming configuration Hypothesis: both directional and nondirectional DBS will significantly improve tremor compared to baseline.

Official Title
-----------------
Directional Versus Nondirectional Deep Brain Stimulation of the VIM Thalamic Nucleus for Essential Tremor: Assessment of Therapeutic Window, Speech, Gait and Balance

Conditions
-----------------
Essential Tremor

Intervention / Treatment
-----------------
* Device: Deep brain stimulation of the VIM Thalamic nuclei


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A tremor syndrome of bilateral upper limb action tremor with at least 3 years' duration Exclusion Criteria: Patients who have decided not to receive DBS for control of their medication-refractory essential tremor. Patients with secondary tremor (ie not Essential Tremor), such as side effects from medications, secondary to another identified neurologic disease (eg multiple sclerosis, -----Parkinson's disease, dystonia). Prior history of deep brain stimulation. Prior history of thalamotomy. A history or signs of dystonia, ataxia or parkinsonism. Task specific tremor. Orthostatic tremor. Patients with cardiac pacemakers, defibrillators, or neurostimulators. Patients who require MRI, ECT, rTMS, or diathermy. Subjects with other type of neurological disease or injury.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blinded crossover design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Directional deep brain stimulation<br>Deep brain stimulation delivered in a directional manner within an axial plane | Device: Deep brain stimulation of the VIM Thalamic nuclei<br>* Deep brain stimulation of the thalamus, in a directional and nondirectional manner<br>|
| Active Comparator: Nondirectional deep brain stimulation<br>Deep brain stimulation delivered in a nondirectional manner within an axial plane | Device: Deep brain stimulation of the VIM Thalamic nuclei<br>* Deep brain stimulation of the thalamus, in a directional and nondirectional manner<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic window | Range of therapeutic current from clinical improvement to side effect threshold, measured in milliamps, within a range of 0.0 to 5.0 milliamps | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of tremor | Change in The Essential Tremor Rating Scale (TETRAS) combined score. Range = 0 to112. Higher score = worse outcome. | 3 months | 
| Compare the effects of directional versus nondirectional DBS on self perception of speech | Self Perception of speech: Subjects will rate their ability to speak on a VAS (from 0 [normal] to 100 mm [worst]) in each condition. | 3 months | 
| Compare the effects of directional versus nondirectional DBS on balance and gait | The Activities-specific Balance Confidence (ABC) scale is a 16-item self-report measure in which participants rate their balance confidence on a 0-100 scale (0 = 0 no confidence, 100 = 100 complete confidence). | 3 months | 
| Compare the effects of directional versus nondirectional DBS on perceptual assessment of voice and speech | Perceptual assessment of voice and speech will be completed with listeners judging a reading sample using a 100mm Visual Analog Scale (VAS). | 3 months |