Algorithms for Programming DBS Systems for ET
Primary Purpose
Essential Tremor
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vim-Deep Brain Stimulation
Sponsored by
About this trial
This is an interventional basic science trial for Essential Tremor
Eligibility Criteria
Inclusion Criteria:
- diagnosis of ET
- medication-refractory tremor
- VIM-DBS implant (unilateral or bilateral)
- 7T MRI pre-operative scan under Dr. Harel's IRB (institutional review board) protocol (#1210M22183)
- Post-operative CT scan
Exclusion Criteria:
- history of musculoskeletal disorders that affect movement of the limbs
- other significant neurological disorder
- prior history of stereotactic neurosurgery (other than VIM-DBS surgery)
- pregnancy
Sites / Locations
- University of MinnesotaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Deep Brain Stimulation
Arm Description
Subjects in this study will have been implanted with a DBS lead in the VIM as part of their routine clinical care and have an existing set of brain MRI's.
Outcomes
Primary Outcome Measures
Therapeutic Windows
Quantify how therapeutic windows (i.e. stimulus amplitude threshold difference between postural and action tremor abolishment and side effect emergence) change over time with human Vim-DBS therapy. During routine clinical evaluation sessions, monopolar stimulation will be applied through each electrode to generate therapeutic window maps and quantify the degree to which stimulus amplitude thresholds for action and postural tremor abolishment and for generating side effects of stimulation (e.g. transient paresthesias) change.
Objective Measures of Tremor
Quantify tasks contained in the Essential Tremor Rating Assessment Scale (TETRAS) scoring system. Inertial measurement units (IMUs) will be attached to the limbs and head of the subject to measure tremor while the subject performs tasks associated with the TETRAS scoring scale. The Archimedes spiral task contained in the TETRAS will be quantified by using a digitizing tablet.
Quality of Life Questionnaire: QUEST
The Quality of life in Essential Tremor Questionnaire (QUEST) questionnaire consists of 30 items that are rated from 0 (never) to 4 (always), corresponding to the frequency with which tremor is perceived to impact function or to be associated with various feelings and attitudes. The 30 items contribute to five sub scales:
Physical/ADL, Psychosocial, Communication, Hobbies/Leisure, and Work/Finances. Each sub scale score is expressed as a percentage of the total score possible, with a higher score indicating greater dissatisfaction with that domain. Total score is computed by calculating the mean of the five sub scale scores. Higher score indicates greater disability.
Quality of Life Questionnaire: TETRAS
The Essential Tremor Rating Assessment Scale (TETRAS) quantifies the impact of essential tremor (ET) on activities of daily living (ADL) and a performance battery. The ADL section consists of 12 items rating the impact of ET on daily activity, each rated 0 (normal) to 4 (severe), with a maximum subscale score of 48. The performance section has 9 items rating action tremor in different areas of the body from 0 (normal) to 4 (severe), with a maximum subscale score of 64. Total score is an unweighted sum of the two subscale scores. Greater total score indicates worse functioning due to ET.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03984643
Brief Title
Algorithms for Programming DBS Systems for ET
Official Title
Algorithms for Programming DBS Systems for ET
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Deep brain stimulation (DBS) targeting the Vim thalamus (ventralis intermedius nucleus) is an FDA-approved neuromodulation therapy for treating postural and action tremor in individuals with essential tremor (ET). The success of this treatment, however, is highly dependent on the ability of clinicians to identify therapeutic stimulation settings through a laborious programming process. There is a strong and growing clinical need for new approaches to provide clinicians with more efficient guidance on how to titrate stimulation settings. This study will leverage subject-specific computational models that can predict neural activation of axonal pathways adjacent to the active electrode(s) and implicated in the therapeutic mechanisms of Vim-DBS to in turn guide clinicians with which stimulation settings are likely to be the most therapeutic on tremor.
Detailed Description
Primary Endpoint/Event/Outcome:
Endpoint: Identify the neural pathways within the brain that are involved in the reduction of action and postural tremor using directional DBS leads and advanced computational optimization algorithms.
Event: Using anatomical segmentation of high-field 7-Tesla MRI and diffusion tensor imaging from 25 human ET subjects, the investigators will build prospective subject-specific, multi-compartment neuron models of the afferent and efferent projections from and to the sensorimotor thalamus. Using these models, the investigators will then apply a semi-automated algorithm that can efficiently identify stimulation settings that most selectively target one pathway over other adjacent pathways. Note that these stimulation settings will not exceed the FDA-approved safety limits that are already programmed into the implanted pulse generator. The optimization algorithm defined stimulation settings will then be tested in human ET subjects to compare the therapeutic efficacy and efficiency of DBS targeting the: interposed-receiving area of motor thalamus, dentate-receiving area of motor. Rendering of a 4-channel DBS lead implant in the VIM nucleus (ventralis intermedius nucleus) of thalamus for treating Essential Tremor.
thalamus, pre-lemniscal radiations (raprl) with medial and lateral divisions, and zona incerta, all of which have been implicated in the therapeutic mechanisms of DBS. This clinical evaluation will occur during routine clinical follow-up sessions in which the Essential Tremor Rating Assessment Scale (TETRAS) will serve as the primary form of qualification scoring of each setting tested.
Outcome: The investigators hypothesize that targeting the interposed-receiving region of motor thalamus and in particular the ascending cerebello-thalamic fibers to this region will result in the strongest and most energy-efficient suppression of action and postural tremor.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Tremor
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
participants will be blinded to the timing of the experimental settings
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Deep Brain Stimulation
Arm Type
Experimental
Arm Description
Subjects in this study will have been implanted with a DBS lead in the VIM as part of their routine clinical care and have an existing set of brain MRI's.
Intervention Type
Device
Intervention Name(s)
Vim-Deep Brain Stimulation
Intervention Description
This study consists of testing additional model-derived DBS settings during initial and regular follow-up clinical visits every 6 months for up to 2 years in which individuals with DBS implants are re-evaluated by a clinician to make sure that the stimulation settings employed during the previous clinical visit remain therapeutic. It is important to note that this study is post-surgical and all procedures (i.e. stimulation settings that will be tested in the clinic) are within the FDA-approved range of stimulation settings available on the implanted pulse generator.
Primary Outcome Measure Information:
Title
Therapeutic Windows
Description
Quantify how therapeutic windows (i.e. stimulus amplitude threshold difference between postural and action tremor abolishment and side effect emergence) change over time with human Vim-DBS therapy. During routine clinical evaluation sessions, monopolar stimulation will be applied through each electrode to generate therapeutic window maps and quantify the degree to which stimulus amplitude thresholds for action and postural tremor abolishment and for generating side effects of stimulation (e.g. transient paresthesias) change.
Time Frame
24-months
Title
Objective Measures of Tremor
Description
Quantify tasks contained in the Essential Tremor Rating Assessment Scale (TETRAS) scoring system. Inertial measurement units (IMUs) will be attached to the limbs and head of the subject to measure tremor while the subject performs tasks associated with the TETRAS scoring scale. The Archimedes spiral task contained in the TETRAS will be quantified by using a digitizing tablet.
Time Frame
24-months
Title
Quality of Life Questionnaire: QUEST
Description
The Quality of life in Essential Tremor Questionnaire (QUEST) questionnaire consists of 30 items that are rated from 0 (never) to 4 (always), corresponding to the frequency with which tremor is perceived to impact function or to be associated with various feelings and attitudes. The 30 items contribute to five sub scales:
Physical/ADL, Psychosocial, Communication, Hobbies/Leisure, and Work/Finances. Each sub scale score is expressed as a percentage of the total score possible, with a higher score indicating greater dissatisfaction with that domain. Total score is computed by calculating the mean of the five sub scale scores. Higher score indicates greater disability.
Time Frame
24-months
Title
Quality of Life Questionnaire: TETRAS
Description
The Essential Tremor Rating Assessment Scale (TETRAS) quantifies the impact of essential tremor (ET) on activities of daily living (ADL) and a performance battery. The ADL section consists of 12 items rating the impact of ET on daily activity, each rated 0 (normal) to 4 (severe), with a maximum subscale score of 48. The performance section has 9 items rating action tremor in different areas of the body from 0 (normal) to 4 (severe), with a maximum subscale score of 64. Total score is an unweighted sum of the two subscale scores. Greater total score indicates worse functioning due to ET.
Time Frame
24-months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
diagnosis of ET
medication-refractory tremor
VIM-DBS implant (unilateral or bilateral)
7T MRI pre-operative scan under Dr. Harel's IRB (institutional review board) protocol (#1210M22183)
Post-operative CT scan
Exclusion Criteria:
history of musculoskeletal disorders that affect movement of the limbs
other significant neurological disorder
prior history of stereotactic neurosurgery (other than VIM-DBS surgery)
pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matthew Johnson, PhD
Phone
6126266492
Email
john5101@umn.edu
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Johnson, PhD
Phone
612-626-6492
Email
john5101@umn.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Algorithms for Programming DBS Systems for ET
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